Recommendations for Patients with Relapsed/Refractory Disease1

PRACTICE AID The Multiple Myeloma Treatment Pyramid: Recommendations for Patients With Relapsed/Refractory Disease1

Therapy for Preiously Treated Myeloma (If a regimen listed here was used as a primary induction therapy and relapse is >6 mo, the same regimen may be repeated)

Category 1 Category • Car lzomib (2 x wk)a/ b • Bortezomib/lenalidomide/dexamethasone dexamethasone a b • Car lzomiba/lenalidomide/ • Car lzomib (weekly) /dexamethasone dexamethasonec • Daratumumabd/bortezomib/ dexamethasone • Daratumumabd/lenalidomide/ Category dexamethasone Preferred regimens • Bendamustine/bortezomib/ • Elotuzumab/lenalidomide/ dexamethasone dexamethasonec • Bendamustine/lenalidomide/ • Ixazomib/lenalidomide/ dexamethasonec dexamethasone ther • Bortezomib/cyclophosphamide/ Category 1 dexamethasone • Car lzomiba/cyclophosphamide/ • Bortezomib/liposomal recommended regimens dexamethasone doxorubicin/dexamethasone • Bortezomib/dexamethasoneb • Cyclophosphamide/lenalidomide/ • lsatuximab-irfc/pomalidomide/ dexamethasone dexamethasone • Daratumumabd • Lenalidomide/ • Daratumumabd/car lzomib/ dexamethasoneb,e dexamethasone • Panobinostat/bortezomib/ seful in certain d circumstances • Daratumumab /pomalidomide/ dexamethasone dexamethasone • Pomalidomide/bortezomib/ • Elotuzumab/bortezomib/ dexamethasone dexamethasone • Pomalidomide/ Category • Elotuzumab/pomalidomide/ b,e dexamethasone • Bendamustine dexamethasone • Car lzomib/cyclophosphamide/ • lxazomib/cyclophosphamide/ Recent pdates in R/R MM thalidomide/dexamethasone dexamethasone • Based on results of the ICARIA-MM trial, • High-dose cyclophosphamide • Ixazomib/dexamethasoneb isatuximab was recently approved by the FDA • Selinexor/dexamethasone • Ixazomib/pomalidomide/ in combination with pom-dex for the treatment Generally reserved for aggressive disease dexamethasone of adults with multiple myeloma who have • Dexamethasone/ • Panobinostat/car lzomiba,b received ≥2 prior therapies, including cyclophosphamide/etoposide/ • Panobinostat/lenalidomide/ 1 lenalidomide and a proteasome inhibitor cisplatin (DCEP) dexamethasone • The XPO1 inhibitor selinexor was recently • Dexamethasone/thalidomide/ • Pomalidomide/cyclophosphamide/ approved for use in patients with R/R MM who cisplatin/doxorubicin/ dexamethasone have received ≥4 prior therapies (including cyclophosphamide/etoposide a patients refractory to ≥2 proteasome inhibitors • Pomalidomide/car lzomib / (DT-PACE) ± bortezomib (VTD-PACE) or IMiDs and an anti-CD38 monoclonal antibody)2 dexamethasone

Clinical Notes • Selected, but not inclusive of all regimens • Frailty assessment should be considered in older adults • Herpes zoster prophylaxis for patients treated with proteasome inhibitors or daratumumab • Subcutaneous bortezomib is the preferred method of administration. Both weekly and twice-weekly dosing schemas may be appropriate and acceptable • Aspirin (81-325 mg) is recommended with immunomodulator-based therapy; therapeutic anticoagulation is recommended for those at high risk for thrombosis • Consideration for appropriate regimen is based on the context of clinical relapse

a Can be used once or twice weekly and at different doses. Can potentially cause cardiac and pulmonary toxicity, especially in elderly patients. b Triplet regimens should be used as the standard therapy for patients with multiple myeloma; however, patients who could not be considered for initiation of treatment with a 3-drug regimen can be started with a 2-drug regimen, with a third drug added once performance status improves. c Clinical trials with these regimens primarily included patients who were lenalidomide-naïve or with lenalidomide-sensitive multiple myeloma. d May interfere with serological testing and cause false-positive indirect Coombs test. Type and screen should be performed before using daratumumab. Includes both daratumumab for IV infusion and daratumumab and hyaluronidase- fihj for subcutaneous injection. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared with daratumumab for IV infusion. e Consider single-agent lenalidomide or pomalidomide for steroid-intolerant individuals. IMiD: immunomodulatory drug; MM: multiple myeloma; NCCN: National Comprehensive Cancer Network; R/R: relapsed/refractory; XPO1: exportin 1. 1. NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. V.4.2020. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. 2.https://www.fda.gov/drugs/resources-information- approved-drugs/fda-grants-accelerated-approval-selinexor-multiple-myeloma. Please consult NCCN guidelines for additional information regarding the regimens listed here, including summary of indications for use. Access the activity, “How I Think, How I Treat: Understanding Innovation in Multiple Myeloma— New Models for Attacking Disease Across the Clinical Spectrum,” at PeerView.com/XBQ40