Clinical Research in Multiple Myeloma: Recent literature – Editors’ picks

Compiled by Efstathios Kastritis, MD
National and Kapodistrian University of Athens

Newly diagnosed MM – Transplant eligible

• Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results. Roussel M, Lauwers-Cances V, Wuilleme S, Belhadj K, Manier S, Garderet L, Escoffre-Barbe M, Mariette C, Benboubker L, Caillot D, Sonntag C, Touzeau C, Dupuis J, Moreau P, Leleu X, Facon T, Hébraud B, Corre J, Attal M.Blood. 2021 Jul 15;138(2):113-121. doi: 10.1182/blood.2021010744.PMID: 33827114
• Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial. Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Allotey D, Shafeek S, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Clinical Studies Group UNHO.Haematologica. 2021 Jul 1;106(7):1957-1967. doi: 10.3324/haematol.2020.247130.PMID: 32499244
• Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. Landgren O, Hultcrantz M, Diamond B, Lesokhin AM, Mailankody S, Hassoun H, Tan C, Shah UA, Lu SX, Salcedo M, Werner K, Rispoli J, Caple J, Sams A, Verducci D, Jones K, Concepcion I, Ciardello A, Chansakul A, Schlossman J, Tavitian E, Shekarkhand T, Harrison A, Piacentini C, Rustad EH, Yellapantula V, Maclaughlan K, Maura F, Landau HJ, Scordo M, Chung DJ, Shah G, Lahoud OB, Thoren K, Murata K, Ramanathan L, Arcila ME, Ho C, Roshal M, Dogan A, Derkach A, Giralt SA, Korde N.JAMA Oncol. 2021 Jun 1;7(6):862-868. doi: 10.1001/jamaoncol.2021.0611.PMID: 3385640

Newly diagnosed transplant ineligible

• Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Facon T, Venner CP, Bahlis NJ, Offner F, White DJ, Karlin L, Benboubker L, Rigaudeau S, Rodon P, Voog E, Yoon SS, Suzuki K, Shibayama H, Zhang X, Twumasi-Ankrah P, Yung G, Rifkin RM, Moreau P, Lonial S, Kumar SK, Richardson PG, Rajkumar SV.Blood. 2021 Jul 1;137(26):3616-3628. doi: 10.1182/blood.2020008787.PMID: 33763699
• Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Larocca A, Bonello F, Gaidano G, D’Agostino M, Offidani M, Cascavilla N, Capra A, Benevolo G, Tosi P, Galli M, Marasca R, Giuliani N, Bernardini A, Antonioli E, Rota-Scalabrini D, Cellini C, Pompa A, Monaco F, Patriarca F, Caravita di Toritto T, Corradini P, Tacchetti P, Boccadoro M, Bringhen S.Blood. 2021 Jun 3;137(22):3027-3036. doi: 10.1182/blood.2020009507.PMID: 33739404
•  Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial. Bringhen S, D’Agostino M, Paris L, Ballanti S, Pescosta N, Spada S, Pezzatti S, Grasso M, Rota-Scalabrini D, De Rosa L, Pavone V, Gazzera G, Aquino S, Poggiu M, Santoro A, Gentile M, Baldini L, Petrucci MT, Tosi P, Marasca R, Cellini C, Palumbo A, Falco P, Hájek R, Boccadoro M, Larocca A.Haematologica. 2020 Jul;105(7):1937-1947. doi: 10.3324/haematol.2019.226407. Epub 2019 Oct 3.PMID: 31582542
•  Sustained Minimal Residual Disease Negativity With Daratumumab in Newly Diagnosed Multiple Myeloma: MAIA and ALCYONE. San-Miguel JF, Avet-Loiseau H, Paiva B, Kumar SK, Dimopoulos MAA, Facon T, Mateos MV, Touzeau C, Jakubowiak AJ, Usmani SZ, Cook G, Cavo M, Quach H, Ukropec J, Ramaswami P, Pei H, Qi M, Sun S, Wang J, Krevvata M, DeAngelis N, Heuck C, Van Rampelbergh R, Kudva A, Kobos R, Qi M, Bahlis NJ.Blood. 2021 Jul 16:blood.2020010439. doi: 10.1182/blood.2020010439. Online ahead of print.PMID: 34269818

Relapsed Myeloma

• Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Špička I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Macé S, Martin T; IKEMA study group. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4.PMID: 34097854
• Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators.Lancet Oncol. 2021 Jun;22(6):801-812. doi: 10.1016/S1470-2045(21)00128-5.PMID: 34087126 Clinical Trial.
• Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse. Dimopoulos M, Weisel K, Moreau P, Anderson LD Jr, White D, San-Miguel J, Sonneveld P, Engelhardt M, Jenner M, Corso A, Dürig J, Pavic M, Salomo M, Casal E, Srinivasan S, Yu X, Nguyen TV, Biyukov T, Peluso T, Richardson P.Leukemia. 2021 Jun;35(6):1722-1731. doi: 10.1038/s41375-020-01021-3. Epub 2020 Sep 7.PMID: 32895455
• Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. Richardson PG, Kumar SK, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Gimsing P, Garderet L, Touzeau C, Buadi FK, Laubach JP, Cavo M, Darif M, Labotka R, Berg D, Moreau P.J Clin Oncol. 2021 Aug 1;39(22):2430-2442. doi: 10.1200/JCO.21.00972. Epub 2021 Jun 11.PMID: 34111952
• Carfilzomib, bendamustine, and dexamethasone in patients with advanced multiple myeloma: The EMN09 phase 1/2 study of the European Myeloma Network. Gay F, Günther A, Offidani M, Engelhardt M, Salvini M, Montefusco V, Patriarca F, Aquino S, Pönisch W, Spada S, Schub N, Gentili S, Wäsch R, Corradini P, Straka C, Palumbo A, Einsele H, Boccadoro M, Sonneveld P, Gramatzki M.Cancer. 2021 Sep 15;127(18):3413-3421. doi: 10.1002/cncr.33647. Epub 2021 Jun 28.PMID: 34181755

Immunotherapy and cellular therapy for myeloma

• Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Sborov D, Suvannasankha A, Weisel K, Voorhees PM, Womersley L, Baron J, Piontek T, Lewis E, Opalinska J, Gupta I, Cohen AD.Cancer. 2021 Jul 27. doi: 10.1002/cncr.33809. Online ahead of print.PMID: 34314018
• Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O’Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S.Lancet. 2021 Jul 24;398(10297):314-324. doi: 10.1016/S0140-6736(21)00933-8. Epub 2021 Jun 24.PMID: 3417502

Minimal Residual Disease

• Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, MAIA. Cavo M, San-Miguel JFF, Usmani SZ, Weisel KC, Dimopoulos MAA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria VTM, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar SK, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi NC.Blood. 2021 Jul 21:blood.2021011101. doi: 10.1182/blood.2021011101. Online ahead of print.PMID: 34289038
• Sustained Minimal Residual Disease Negativity With Daratumumab in Newly Diagnosed Multiple Myeloma: MAIA and ALCYONE. San-Miguel JF, Avet-Loiseau H, Paiva B, Kumar SK, Dimopoulos MAA, Facon T, Mateos MV, Touzeau C, Jakubowiak AJ, Usmani SZ, Cook G, Cavo M, Quach H, Ukropec J, Ramaswami P, Pei H, Qi M, Sun S, Wang J, Krevvata M, DeAngelis N, Heuck C, Van Rampelbergh R, Kudva A, Kobos R, Qi M, Bahlis NJ.Blood. 2021 Jul 16:blood.2020010439. doi: 10.1182/blood.2020010439. Online ahead of print.PMID: 34269818

Prognosis – Genetics

•  The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma. Sharma N, Smadbeck JB, Abdallah N, Zepeda-Mendoza C, Binder M, Pearce KE, Asmann YW, Peterson JF, Ketterling RP, Greipp PT, Bergsagel PL, Rajkumar SV, Kumar SK, Baughn LB.Clin Cancer Res. 2021 Jul 7. doi: 10.1158/1078-0432.CCR-21-0005. Online ahead of print.PMID: 34233962
• Cereblon Enhancer Methylation and IMiD Resistance in Multiple Myeloma. Haertle L, Barrio S, Munawar U, Han S, Zhou X, Vogt C, Alonso R, Bittrich M, Ruiz-Heredia Y, Da-Via M, Zovko J, Garitano-Trojaola A, Bolli N, Ruckdeschel A, Stühmer T, Chatterjee M, Kull M, Krönke J, Agirre X, Martin-Subero I, Raab P, Einsele H, Rasche L, Martinez-Lopez J, Haaf T, Kortüm KM.Blood. 2021 Jun 11:blood.2020010452. doi: 10.1182/blood.2020010452. Online ahead of print.PMID: 3411583

AL Amyloidosis

• Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.
  Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators.N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631.PMID: 34192431 Clinical Trial.
• A randomized phase 3 study of ixazomib-dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis. Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G.Leukemia. 2021 Jun 24. doi: 10.1038/s41375-021-01317-y. Online ahead of print.PMID: 34168284