Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Multiple Myeloma Cancer Immunotherapy Guideline Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines.

Update 2-1-2022

Based on the FDA approval of daratumumab in combination with carfilzomib and dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy on November 30, 2021, the Multiple Myeloma CPG has been updated in the following locations: * Monoclonal Antibodies Expert Panel Recommendations * Multiple Myeloma Key Monoclonal Antibody Therapies Trials

Reference: Daratumumab + hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) and carfilzomib (Kyprolis, Amgen, Inc.) plus dexamethasone press release

Update 4-9-2021

Based on the approval of idecabtagene vicleucel for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, the Multiple Myeloma CPG has been updated in the following locations: * Background * CAR T cell Therapies

Reference: Idecabtagene vicleucel (ABECMA) FDA press release

Based on the approval of isatuximab-irfc in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, the Multiple Myeloma CPG has been updated in the following locations: * Monoclonal Antibody Therapies * Multiple Myeloma Key Monoclonal Antibody Therapies Trials

Reference: Isatuximab-irfc (SARCLISA) FDA press release

Update 8-5-2020

Based on the accelerated approval of belantamab mafodotin-blmf for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent, the Multiple Myeloma CPG was updated in the following locations: * Antibody-Drug Conjugates * Background

Reference: Belantamab mafodotin-blmf (BLENREP) FDA press release

Update 4-9-2021

Information on idecabtagene vicleucel approval data and indication has been added, as noted below:

• Idecabtagene vicleucel is a BCMA-directed CAR T cell therapy, indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on safety and efficacy in a multicenter study of 127 patients with relapsed and refractory multiple myeloma who had received at least three prior lines of antimyeloma therapies with 88% having received four or more prior lines of therapies. Efficacy was evaluated in 100 patients who received idecabtagene vicleucel at a dose range of 300 to 460 x 106 CAR-positive T cells. The ORR (by IMWG criteria) was 72% (95% CI, 62% to 81%) and CR rate was 28% (95% CI, 19% to 38%). An estimated 65% of patients who achieved CR remained in CR for at least 12 months. The expert panel recommendations on CAR T cell therapy for multiple myeloma were developed, in part, based on experience from trials of idecabtagene vicleucel.

Update 8-5-2020

A recommendation has been added, as noted below:

• Avoid use of contact lenses unless directed by an opthamologist during treatment with belantamab mafadotin.

Update 8-5-2020

The following recommendation has been removed:

• During belantamab mafodotin treatment specifically, therapy can be restarted once keratopathy or other AEs (such as cytopenias) have resolved to grade 1 or less. Dose reduction from 3.4 to 2.5 mg/kg may be considered. Further dose reductions to 1.9 mg/kg may be done if significant toxicity recurs.

Update - 8-5-2020

A recommendation was updated, as noted below:

• Belantamab mafadotin should be withheld in the event of moderate to severe corneal toxicity, then restarted with a reduced dose once symptoms resolve

Update 8-5-2020

A recommendation was updated, as noted below:

• Patients being treated with belentamab mafadotin should be advised to use preservative-free eye drops at least 4 times per day starting with the first infusion and continuing until end of treatment.

Update 8-5-2020

A recommendation was updated, as noted below:

• Patients should be routinely monitored with complete blood counts and complete metabolic panels.

Update 8-5-2020

An additional recommendation was added, as noted below:

• Belantamab mafadotin is approved for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 mAb, a proteasome inhibitor and an immunomodulatory agent

Update 8-5-2020

The approval status and information regarding Belantamab mafadotin has been updated, as noted below:

• Belantamab mafadotin, an anti-BCMA antibody conjugated to the cytotoxic monomethyl auristatin F via a non-cleavable linker, received accelerated approval for relapsed or refractory multiple myeloma in August, 2020. Approval was based on the open-label, multicenter trial DREAMM-2 (NCT 03525678). Because of the risks of ocular toxicity, belantamab mafodotin is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS.