Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial

Facon, Thierry; Kumar, Shaji; Plesner, Torben; Orłowski, Robert Z.; Moreau, Philippe; Bahlis, Nizar J.; Basu, Supratik; Nahi, Hareth; Hulin, Cyrille; Quach, Hang; Goldschmidt, Hartmut; O’Dwyer, Michael; Perrot, Aurore; Venner, Christopher P.; Weisel, Katja; Mace, Joseph R.; Raje, Noopur; Tiab, Mourad; Macro, Margaret; Frenzel, Laurent; Leleu, Xavier; Ahmadi, Tahamtan; Wang, Jianping; Rampelbergh, Rian Van; Uhlar, Clarissa M.; Tromp, Brenda; Delioukina, Maria; Vermeulen, Jessica; Usmani, Saad Z.

doi:10.1016/s1470-2045(21)00466-6

Cited by 198 publications

(157 citation statements)

References 29 publications

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“…44,45 Among elderly patients (age > 75 years), median OS is lower, and is approximately 5 years. 42,46 These numbers likely underestimate current survival probabilities since they predate the arrival of monoclonal antibodies and several other new agents that have been introduced in the last 5 years. On the other hand, they may be overestimates of the true population-based survival since they are derived from randomized controlled trials where patients with poor performance status and comorbidities are typically excluded.…”

Section: Prognosis and Risk Stratificationmentioning

confidence: 99%

“…In the subset of patients eligible for ASCT, 4‐year survival rates are more than 80% 43 ; the median overall survival (OS) among these patients is more than 8 years 44,45 . Among elderly patients (age > 75 years), median OS is lower, and is approximately 5 years 42,46 . These numbers likely underestimate current survival probabilities since they predate the arrival of monoclonal antibodies and several other new agents that have been introduced in the last 5 years.…”

Section: Prognosis and Risk Stratificationmentioning

confidence: 99%

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Multiple myeloma: 2022 update on diagnosis, risk stratification, and management

2022

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Disease Overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis:The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsyproven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Risk Stratification:The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. The presence of any two high risk factors is considered double-hit myeloma, and three or more high risk factors is triple-hit myeloma.Risk-Adapted Initial Therapy: In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard-risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.Maintenance Therapy: Standard-risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma.Management of Relapsed Disease: A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.

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Section: Prognosis and Risk Stratificationmentioning

confidence: 99%

Section: Prognosis and Risk Stratificationmentioning

confidence: 99%

Multiple myeloma: 2022 update on diagnosis, risk stratification, and management

2022

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“…The PFS improvement was also seen with DRd in patients with high‐risk cytogenetics—del(17p), t(4;14), and t(14;16) (HR = 0.55, 95% CI: 0.32–0.94). Median OS was not reached in either group, but the hazard ratio favored the daratumumab group versus Rd (HR = 0.68, 95% CI: 0.53–0.86) 65 . The most common adverse events associated with DRd versus Rd were neutropenia (54% vs. 37%), pneumonia (19% vs. 11%), anemia (17% vs. 22%), and lymphopenia (16% vs. 11%).…”

Section: Treatment Of Ndmmmentioning

confidence: 95%

“…Complete response (26% vs. 14%, p < .01) and ≥VGPR (63% vs. 48%, p < .01) rates were higher with IRd than with placebo-Rd. 25 65 The most common adverse events associated with DRd versus Rd were neutropenia (54% vs. 37%), pneumonia (19% vs. 11%), anemia (17% vs. 22%), and lymphopenia (16% vs. 11%). Although DRd has not been compared with VRd in trials, an indirect comparison found that DRd was associated with a lower risk of disease progression or death, as compared to VRd (HR = 0.68, 95% CI: 0.48-0.98).…”

Section: Multidrug Regimensmentioning

confidence: 99%

Current approaches to management of newly diagnosed multiple myeloma

2022

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Major developments in the treatment of multiple myeloma (MM) over the past decade have led to a continued improvement in survival. Significant progress has been made with deeper and longer remissions seen with newer treatment approaches—both for induction as well as maintenance therapy. The treatment approach to MM is guided by several factors including patient age, frailty, comorbidities, eligibility for autologous stem cell transplantation (ASCT), and risk stratification into standard‐risk or high‐risk MM. High‐risk MM is defined by the presence of t(4;14), t(14;16), t(14;20), del (17p), TP53 mutation, or gain (1q). Transplant eligible patients should receive 4–6 cycles of induction followed by stem cell collection. Patients can then undergo ASCT, or continue induction therapy and shift to maintenance, delaying ASCT till first relapse. Transplant ineligible patients should receive induction therapy followed by maintenance. For induction therapy prior to ASCT, a proteasome inhibitor‐IMiD combination remains standard with monoclonal antibody‐based quadruplets preferred in high‐risk patients. Among transplant ineligible patients, those with standard‐risk MM should receive DRd continued until disease progression, while bortezomib containing regimens (VRd or VRd lite) can be considered for high‐risk patients. Finally, standard‐risk patients should receive lenalidomide maintenance after induction/ASCT, while proteasome inhibitor‐IMiD combinations should be used for high‐risk patients.

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“…Other treatment options are lenalidomide, thalidomide, and bortezomib with a manageable toxicity profile. For POEMS, cases not included in POLLUX 6 and MAIA, 7 the major studies that demonstrated the superiority of DRd compared with lenalidomide and dexamethasone in multiple myeloma, DRd is considered as a very promising therapy choice.…”

mentioning

confidence: 99%