TREATMENT LANDSCAPE: MULTIPLE MYELOMA
About multiple myeloma
Multiple myeloma (MM) is a rare, severe heterogeneous cancer, with ~73% of non-transplant newly diagnosed MM (NDMM) patients developing relapsed or refractory disease within 5 years1-4
~73% of patients with non-transplant NDMM relapse or become refractory to treatment within 5 years3
The incidence of MM is trending upward in the United States1
The median age at diagnosis is 69 years1
The majority of patients with NDMM in the United States do not receive
a transplant7
Estimated number of patients with NDMM who did not receive a transplant in 20241,3,7
Determining whether a patient receives a transplant takes into account a variety of myeloma- and patient-related factors, including8,9:
- Stage and aggressiveness of disease
-
Age
-
Comorbidities
-
Performance status
-
Patient preference
aThe Surveillance, Epidemiology, and End Results (SEER) program defines MM as including smoldering (asymptomatic) plasma cell myeloma, non-secretory plasma cell myeloma,
and plasma cell leukemia. Therefore, the number of newly diagnosed cases (35,780) was adjusted by removing the estimated number of patients with smoldering MM (11.9%) from
the number of NDMM cases.
Response to 1L therapy and attaining prolonged initial remission is an
important prognostic factor in patients with NDMM10
Progression to subsequent lines of therapy leads to reduced responses to treatment, higher treatment discontinuation, and increased medical costs11,12
Only ~43% of non-transplant NDMM patients go on to receive second-line (2L) therapy.13
Total all-cause medical costs associated with MM treatment are high and increase with each successive line of therapy.12
aCR+ includes CR and stringent CR. Observational study analyzed real-world data between 2008 and 2013.
bTotal cost includes outpatient visits, MM-related medical costs, anti-MM pharmacy drug costs, inpatient visits, emergency department costs, and supportive care.
1L, first line; 2L, second line; 3L, third line; 4L, fourth line; CR, complete response; MM, multiple myeloma; ORR, overall response rate; PMPM, per member per month; VGPR, very good partial response.
Disease progression in patients with non-transplant NDMM may result in inpatient costs up to 2 times higher than in patients without disease progression14
Potential adverse events secondary to MM progression that may increase costs of care include:
Renal Impairment
Incidence of renal impairment increases as
the disease becomes more refractory and
patients progress through lines of therapy15
Severe skeletal-related events (SREs)
Up to 90% of patients with MM experience osteolytic bone lesions, which may lead to SREs16
Sepsis17
This information is intended solely to highlight the economic burden of disease and does not imply any specific clinical outcomes.
aProgression was defined as advancement to the next line of therapy; evidence of bone metastasis, hypercalcemia, soft tissue plasmacytoma, SRE fractures, acute kidney failure,
and renal failure while off therapy; or death within the first 12 months after initiation of therapy.
1L, first line; NDMM, newly diagnosed multiple myeloma.
Poor prognostic factors such as older age, ISS stage III disease, and a high-risk cytogenetic profile can contribute to worse outcomes1,21,22
~65% of patients with MM are aged ≥65 years1,6
Up to 39% of patients with NDMM have ISS stage III disease22,23
Up to 40% of patients with NDMM have a high-risk cytogenetic profile24
ISS, International Staging System; PFS, progression-free survival; R-ISS, Revised ISS.
There remains an opportunity to help improve outcomes in patients with NDMM who do not receive a transplant
Patients with NDMM have an
estimated 5-year relative survival rate of ~61%1
After discontinuing 1L therapy, only ~43% go on to receive 2L therapy due to death or other causes1
Overall survival, PFS, and response
to treatment diminish with each
successive line of therapy13
Clinical profile of SARCLISA
Review the clinical trial results for patients with
newly diagnosed and relapsed or refractory MM.
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References: 1. Cancer stat facts: myeloma. National Cancer Institute. SEER program. Accessed January 7, 2025. https://seer.cancer.gov/statfacts/html/mulmy.html 2. Schavgoulidze A, Cazaubiel T, Perrot A, Avet-Loiseau H, Corre J. Multiple myeloma: heterogeneous in every way. Cancers (Basel). 2021;13(6):1285. doi:10.3390/cancers13061285 3. US Multiple Myeloma. CancerMPact® Treatment Architecture [database online]. Oracle; 2023. Accessed May 30, 2024. 4. Padala SA, Barsouk A, Barsouk A, et al. Epidemiology, staging, and management of multiple myeloma. Med Sci (Basel). 2021;9(1):3. doi:10.3390/medsci9010003 5. Multiple myeloma. National Organization for Rare Disorders. Updated February 6, 2023. Accessed January 7, 2025. https://rarediseases.org/rare-diseases/multiple-myeloma/ 6. SEER*Explorer. National Cancer Institute. SEER program. Updated November 5, 2024. Accessed January 7, 2025. https://seer.cancer.gov/statistics-network/explorer/application.html 7. Richter J, Pan D, Salinardi T, Rice MS. Real-world multiple myeloma front-line treatment and outcomes by transplant in the United States. EJHaem. 2023;4(4):984-994. doi:10.1002/jha2.739 8. Understanding Stem Cell Transplant in Myeloma. International Myeloma Foundation. November 2024. Accessed January 7, 2025. https://www.myeloma.org/resource-library/understanding-stem-cell-transplant-myeloma 9. Grant SJ, Mian HS, Giri S, et al. Transplant-ineligible newly diagnosed multiple myeloma: current and future approaches to clinical care. J Geriatr Oncol. 2021;12(4):499-507. doi:10.1016/j.jgo.2020.12.001 10. Hagen P, Zhang J, Barton K. High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions. Blood Cancer J. 2022;12(5):83. doi:10.1038/ s41408-022-00679-5 11. Verelst SGR, Blommestein HM, De Groot S, et al. Long-term outcomes in patients with multiple myeloma: a retrospective analysis of the Dutch Populationbased HAematological Registry for Observational Studies (PHAROS). Hemasphere. 2018;2(4):e45. doi:10.1097/HS9.0000000000000045 12. MacEwan JP, Batt K, Yin W, et al. Economic burden of multiple myeloma among patients in successive lines of therapy in the United States. Leuk Lymphoma. 2018;59(4):941-949. doi:10.1080/10428194.2017.1361035 13. Fonseca R, Usmani SZ, Mehra M, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer. 2020;20(1):1087. doi:10.1186/s12885-020-07503-y 14. Hagiwara M, Panjabi S, Delea T, Yucel E, Fonseca R. Burden of disease progression in patients with multiple myeloma in the US. Leuk Lymphoma. 2020;61(1):47-55. doi:10.1080/10428194.2019.1648802 15. Hari P, Romanus D, Luptakova K, et al. The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies. J Geriatr Oncol. 2018;9(2):138-144. doi:10.1016/j.jgo.2017.09.007 16. Walker RE, Lawson MA, Buckle CH, Snowden JA, Chantry AD. Myeloma bone disease: pathogenesis, current treatments and future targets. Br Med Bull. 2014;111(1):117-138. doi:10.1093/bmb/ldu016 17. Garnica M. Multiple myeloma and infection: this association is still close. Hematol Transfus Cell Ther. 2019;41(4):281-282. doi:10.1016/j.htct.2019.09.002 18. Bhowmik D, Song X, Intorcia
M, Kent ST, Shi N. Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma. J Oncol Pharm Pract. 2019;25(4):855-864. doi:10.1177/1078155218766408 19. Barlev A, Song X, Ivanov B, Setty V, Chung K. Payer costs for inpatient treatment of pathologic fracture, surgery to bone, and spinal cord compression among patients with multiple myeloma or bone metastasis secondary to prostate or breast cancer. J Manag Care Pharm. 2010;16(9):693-702. doi:10.18553/jmcp.2010.16.9.693 20. Moturi KR, Lingamaneni P, Vohra I, Baral B, Farooq MZ, Batra K. Outcomes of sepsis in patients with multiple myeloma. J Clin Oncol. 2020;38(15) (suppl):e20513. doi:10.1200/JCO.2020.38.15_suppl.e205 21. Bisht K, Walker B, Kumar SK, et al. Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies. Expert Rev Hematol. 2021;14(12):1099-1114. doi:10.1080/17474086.2021.1983427 22. Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-3420. doi:10.1200/JCO.2005.04.242 23. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33(26):2863-2869. doi:10.1200/JCO.2015.61.2267 24. Hanamura I. Multiple myeloma with high-risk cytogenetics and its treatment approach. Int J Hematol. 2022;115(6):762-777. doi:10.1007/s12185-022-03353-5 25. Caro J, Al Hadidi S, Usmani S, Yee AJ, Raje N, Davies FE. How to treat high-risk myeloma at diagnosis and relapse. Am Soc Clin Oncol Educ Book. 2021;41:291-309. doi:10.1200/EDBK_320105
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
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