Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies

Mateos, María Victoria; Spencer, Andrew; Nooka, Ajay K.; Pour, Luděk; Weisel, Katja; Cavo, Michèle; Laubach, Jacob P.; Cook, Gordon; Iida, Shinsuke; Benboubker, Lotfi; Usmani, Saad Z.; Yoon, Sung Soo; Bahlis, Nizar J.; Chiu, Christopher; Ukropec, Jon; Schecter, Jordan M.; Qin, Xiang; O’Rourke, Lisa; Dimopoulos, Meletios A.

doi:10.3324/haematol.2019.217448

Cited by 46 publications

(51 citation statements)

References 29 publications

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“…Furthermore, inferior outcomes may also be associated with a lack of a more personalised regimen selection. For example, similar outcomes have been reported in the >75 years old patient cohort in both the POLLUX and CASTOR trials [10]. Treatment strategies for patients deemed TNE have evolved and it is clear that improvements in survival have been less impressive in this group of patients [7,11].…”

Section: Introduction-the Unmet Needmentioning

confidence: 55%

Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network

et al. 2020

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As the treatment landscape continues to evolve towards the application of precision medicine in multiple myeloma (MM), there is a clear need to identify those patients who are at risk of not achieving the maximum benefit whilst exposed to the highest level of toxicity. This group of patients, defined as frail, is an unmet clinical need. However, how we define such a vulnerable group of patients with MM remains to be clarified. An integral aspect of this is to define the physiological age and capacity of patients with MM to deal with the burden of their disease and it's treatment. Such assessments may include not only functional and clinical assessments but also laboratory-based biomarkers of frailty, aging and senescent cellular burden. A need to develop, test and validate clinical screening scores before their adoption into clinical practice is mandated. This position paper from the European Myeloma Network aims to review what is known about defining frailty in MM, and how we can advance this knowledge for the design of clinical trials and ultimately how we deliver treatment in the clinic.

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Section: Introduction-the Unmet Needmentioning

confidence: 55%

Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network

et al. 2020

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“…Updated results of this trial after 19.4 months of median follow up revealed that the PFS benefit of DVd was most apparent in patients with a single prior line of therapy (median: not reached versus 7.9 months; P < 0.0001); a possible OS benefit was observed in this group of patients [26,27]. DVd was also superior to Vd in subgroups based on prior treatment exposure, lenalidomide-refractory status, time since last therapy, cytogenetic risk, or age [28]. At a median follow up of 40 months DVd, still prolonged PFS vs Vd in both patients with high (median 13.4 vs 7.2 months, P = 0.0002) and standard (median 18.4 vs 6.8 months P < 0.0001) cytogenetic risk [29].…”

Section: Daratumumab In Combination With Pismentioning

confidence: 88%

“…After a median follow up of 44.3 months DRd still prolonged PFS vs Rd in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35-0.55; P < 0.0001), independently upon cytogenetic risk (high-risk: 26.8 vs 8.8 months, P = 0.01; standard risk: not reached vs 19.9 months, P < 0.0001), number of prior lines of therapy, different treatment-free intervals, and age [28,38]. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P < 0.01).…”

Section: Daratumumab In Combination With Imidsmentioning

confidence: 98%

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

Musto

Rocca

2020

Expert Review of Hematology

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Introduction: In the last few years, monoclonal antibodies have rapidly modified the therapeutic strategies for treating patients with multiple myeloma. Areas covered: In this review, the most recent literature data regarding indications for which monoclonal antibodies are currently or will be shortly approved as salvage therapies in relapsed/refractory myeloma are discussed. In particular, updated results until March 22, 2020 of antibodies directed against CD38 (daratumumab and isatuximab), SLAMF7 (elotuzumab), BCMA (GSK2857916/belantamab mafodotin), and PD-1/PD-1 L axis (nivolumab and pembrolizumab) will be analyzed in detail. Expert opinion: Monoclonal antibodies represent a new, very effective approach that will open novel and dynamic treatment scenarios for myeloma patients in the coming years. Optimal positioning and selection of different antibodies that are or will be soon available, appropriate combinations and careful evaluation of possible new toxicities should be considered in the future management of these patients.

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“…The landscape of treatment options for relapse/refractory multiple myeloma (MM) continues to evolve dramatically. The advent of new generations of proteasome inhibitors (PI) [1,2], immunomodulatory drugs (IMiD) and now immunotherapies [3][4][5][6] has considerably improved survival. Unfortunately, however, these agents do not definitely eliminate MM cells and MM remains fundamentally an incurable disease.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant?

Park

Byun

Yoon

et al. 2020

JCM

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Background: Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear. Methods: Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017. Results: The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%). Conclusion: AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.

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Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies

Cited by 46 publications

References 29 publications

Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network

Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant?

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