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Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

ABSTRACT: Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.

SUBMITTER: Lahuerta JJ

PROVIDER: S-EPMC5568033 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

Lahuerta Juan-Jose JJ Paiva Bruno B Vidriales Maria-Belen MB Cordón Lourdes L Cedena Maria-Teresa MT Puig Noemi N Martinez-Lopez Joaquin J Rosiñol Laura L Gutierrez Norma C NC Martín-Ramos María-Luisa ML Oriol Albert A Teruel Ana-Isabel AI Echeveste María-Asunción MA de Paz Raquel R de Arriba Felipe F Hernandez Miguel T MT Palomera Luis L Martinez Rafael R Martin Alejandro A Alegre Adrian A De la Rubia Javier J Orfao Alberto A Mateos María-Victoria MV Blade Joan J San-Miguel Jesus F JF

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20170512 25

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievem ...[more]

PMID: 28498784

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Project description:BackgroundPatients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear.ObjectivesThis study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations.DesignA posthoc analysis of individual-participant level data (IPD).MethodsIPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark.ResultsAmong 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26-0.77), p = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations.ConclusionThis study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM.Trial registrationMAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).

Dataset Information

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

Publications

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

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