DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma

Thibaud Prawitz, Rakesh Popat, Attaya Suvannasankha, Grammati Sarri, Rachel Hughes, Feng Wang, Cosmina Hogea, Shannon Allen Ferrante, Boris Gorsh, Jenny Willson, Venediktos Kapetanakis, Thibaud Prawitz, Rakesh Popat, Attaya Suvannasankha, Grammati Sarri, Rachel Hughes, Feng Wang, Cosmina Hogea, Shannon Allen Ferrante, Boris Gorsh, Jenny Willson, Venediktos Kapetanakis

Abstract

Introduction: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).

Methods: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH).

Results: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3-4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001).

Conclusion: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.

Keywords: Belamaf; Indirect treatment comparison; MAIC; MAMMOTH; Matching-adjusted; RRMM; Selinexor; Survival.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
PRISMA diagram. aThe scope of the SLR was wider than the inclusion criteria of the DREAMM-2 study in order to provide an overview of the treatment landscape. bKey comparators to belantamab mafodotin included the following treatments administered as mono- or combination therapies: bortezomib, carfilzomib, daratumumab, dexamethasone, elotuzumab, ixazomib, lenalidomide, pomalidomide, and selinexor. PI, proteasome inhibitor; RRMM, relapsed or refractory multiple myeloma; SLR, systematic literature review; ITC, indirect treatment comparisons
Fig. 2
Fig. 2
OS (A), DoR (B) and PFS (C) Kaplan-Maier plots for belamaf 2.5 mg/kg (DREAMM-2) observed and MAIC adjusted versus sel + dex (STORM Part 2). (D) OS versus SoC from the MAMMOTH study (overlay of the estimates from different sources). Belamaf, belantamab mafodotin; DoR, duration of response; MAIC, matching-adjusted indirect comparison; OS, overall survival; PFS, progression-free survival; sel + dex, selinexor plus dexamethasone
Fig. 3
Fig. 3
Breakdown of patients per response type in the belamaf cohort before and after base case population adjustment from DREAMM-2 and in the observed sel + dex cohort from STORM Part 2. Belamaf, belantamab mafodotin; CR, complete response; ORR, overall response rate; OS, overall survival; PR, partial response; sCR, stringent complete response; sel + dex, selinexor plus dexamethasone; VGPR, very good partial response
Fig. 4
Fig. 4
Summary of the comparative safety of belamaf versus sel + dex before and after MAIC adjustment using all MAIC models. A Hematologic and B non-hematologic adverse events. aIncludes the preferred terms thrombocytopenia, platelet count decreased; bincludes the preferred terms lymphopenia, lymphocyte count decreased; cincludes the preferred terms fatigue and asthenia. OR < 1 favors belamaf; OR < 0.5, risk 50% lower with belamaf. TEAEs highlighted in gray boxes were significantly different. Belamaf, belantamab mafodotin; CI, confidence interval; MAIC, matching adjusted indirect comparison; sel + dex, selinexor plus dexamethasone; TEAE, treatment-related adverse events

References

    1. Kazandjian D. Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol. 2016;43:676–681. doi: 10.1053/j.seminoncol.2016.11.004.
    1. Robak P, Drozdz I, Szemraj J, Robak T. Drug resistance in multiple myeloma. Cancer Treat Rev. 2018;70:199–208. doi: 10.1016/j.ctrv.2018.09.001.
    1. Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2016;91:101–119. doi: 10.1016/j.mayocp.2015.11.007.
    1. Podar K, Shah J, Chari A, Richardson PG, Jagannath S. Selinexor for the treatment of multiple myeloma. Expert Opin Pharmacother. 2020;21:399–408. doi: 10.1080/14656566.2019.1707184.
    1. Sonneveld P, De Wit E, Moreau P. How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? Crit Rev Oncol Hematol. 2017;112:153–170. doi: 10.1016/j.critrevonc.2017.02.007.
    1. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79:867–874. doi: 10.4065/79.7.867.
    1. Yong K, Delforge M, Driessen C, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol. 2016;175:252–264. doi: 10.1111/bjh.14213.
    1. Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33:2266–2275. doi: 10.1038/s41375-019-0435-7.
    1. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21:207–221. doi: 10.1016/S1470-2045(19)30788-0.
    1. Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7:1187–1199. doi: 10.2217/imt.15.77.
    1. Lonial S, Lee H, Badros A, et al. The American Society for Clinical Oncology (ASCO) Congress; May 29–31, 2020; Virtual Format: ASCO; 2020.
    1. GlaxoSmithKline, Research Triangle Park, NC. BLENREP prescribing information. 2020. .
    1. European Medicines Agency (EMA). BLENREP 100 mg powder [Summary of Product Characteristics]; 2020. .
    1. Phillippo DM, AE A, Dias S, Palmer S, Abrams KR, Welton NJ. NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE. 2016. . Accessed 2 Apr 2020.
    1. Hughes R, Sarri G, Kapetanakis V, et al. Clinical outcomes in late-line relapsed/refractory multiple myeloma: systematic literature review [unpublished manuscript]. Evidera, San Francisco, CA, USA 2021.
    1. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381:727–738. doi: 10.1056/NEJMoa1903455.
    1. Costa LJ, Hari P, Kumar SK, et al. Overall survival of triple class refractory, penta-exposed multiple myeloma (MM) patients treated with selinexor plus dexamethasone or conventional care: a combined analysis of the STORM and mammoth studies. Blood. 2019;134:3125. doi: 10.1182/blood-2019-124991.
    1. Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50:683–691. doi: 10.1016/S0895-4356(97)00049-8.
    1. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–e346. doi: 10.1016/S1470-2045(16)30206-6.
    1. Vogl DT, Dingli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36:859–866. doi: 10.1200/JCO.2017.75.5207.
    1. Chari A, Vogl DT, Dimopoulos M, et al., editors. Results of the pivotal STORM study (Part 2): deep and durable responses with oral selinexor plus low dose dexamethasone in patients with penta-exposed and triple class refractory MM. 62nd American Society of Hematology Annual Meeting & Exposition 2018; San Diego, CA, USA.
    1. Jagannath S, Vogl DT, Dimopoulos M, et al., editors. Efficacy of oral selinexor plus low dose dexamethasone (Sd) in patients with penta-refractory myeloma: results of the pivotal STORM Part II Study. 6th Annual Meeting: Society of Hematologic Oncology; 2018; Houston, TX, USA.
    1. Food and Drug Administration (FDA). Multi-discipline review of selinexor (proposed trade name: XPOVIO®) application number 212306Orig1s000; 2019. . Accessed Apr 2020.
    1. Farooq AV, Degli Esposti S, Popat R, et al. Corneal epithelial findings in patients with multiple myeloma treated with antibody-drug conjugate belantamab mafodotin in the pivotal, randomized, DREAMM-2 study. Ophthalmol Ther. 2020;9(4):889–911. doi: 10.1007/s40123-020-00280-8.
    1. Gastanaga VM, Schwartzberg LS, Jain RK, et al. Prevalence of hypercalcemia among cancer patients in the United States. Cancer Med. 2016;5:2091–2100. doi: 10.1002/cam4.749.
    1. Eaton JS, Miller PE, Mannis MJ, Murphy CJ. Ocular adverse events associated with antibody-drug conjugates in human clinical trials. J Ocul Pharmacol Ther. 2015;31:589–604. doi: 10.1089/jop.2015.0064.
    1. Kapetanakis V, Prawitz T, Schlichting M, et al. Assessment-schedule matching in unanchored indirect treatment comparisons of progression-free survival in cancer studies. Pharmacoeconomics. 2019;37:1537–1551. doi: 10.1007/s40273-019-00831-3.
    1. Rajkumar SV. Updated diagnostic criteria and staging system for multiple myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418–e423. doi: 10.1200/EDBK_159009.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel