How I Treat Relapsed Multiple Myeloma

Blood ◽  
2022 ◽  
Author(s):  
Efstathios Kastritis ◽  
Evangelos Terpos ◽  
Meletios A. Dimopoulos
Keyword(s):  
Multiple Myeloma ◽  
Critical Factor ◽  
First Line ◽  
Incurable Disease ◽  
Drug Classes ◽  
Key Factor ◽  
Choice Of Treatment ◽  
Drug Regimens ◽  
Relapsed Disease ◽  
Choice Of Therapy

Despite recent advances multiple myeloma remains an incurable disease for most of the patients and initial remission will be followed by relapses requiring therapy. For many, there will be several remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first line remain the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first line and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first line and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improves outcomes and overcomes class resistance but, until now, while the biology is important, can offer only limited guidance for the choice of therapy.

scholarly journals Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3106
Author(s):  
Francesca Bonello ◽  
Mario Boccadoro ◽  
Alessandra Larocca
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Treatment Options ◽  
Real Life ◽  
Frailty Status ◽  
Frail Patients ◽  
Multidimensional Evaluation ◽  
Choice Of Treatment ◽  
Choice Of Therapy

Multiple myeloma (MM) mostly affects elderly patients, which represent a highly heterogeneous population. Indeed, comorbidities, frailty status and functional reserve may vary considerably among patients with similar chronological age. For this reason, the choice of treatment goals and intensity is particularly challenging in elderly patients, and it requires a multidimensional evaluation of the patients and the disease. In recent years, different tools to detect patient frailty have been developed, and the International Myeloma Working Group frailty score currently represents the gold standard. It identifies intermediate-fit and frail patients requiring gentler treatment approaches compared to fit patients, aiming to preserve quality of life and prevent toxicities. This subset of patients is underrepresented in clinical trials, and studies exploring frailty-adapted approaches are scarce, making the choice of therapy extremely challenging. Treatment options for intermediate-fit and frail patients might include dose-adapted combinations, doublets, and less toxic combinations based on novel agents. This review analyzes the available tools for the assessment of frailty and possible strategies to improve the discriminative power of the scores and expand their use in real-life and clinical trial settings. Moreover, it addresses the main therapeutic challenges in the management of intermediate-fit and frail MM patients at diagnosis and at relapse.

scholarly journals Bendamustine-Based Regimens as Salvage Therapy in Refractory/Relapsed Multiple Myeloma Patients: A Retrospective Real-Life Analysis by the Polish Myeloma Group

2021 ◽  
Vol 10 (23) ◽  
pp. 5504
Author(s):  
Norbert Grzasko ◽  
Grzegorz Charlinski ◽  
Marta Morawska ◽  
Pawel Kicinski ◽  
Anna Waszczuk-Gajda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Real Life ◽  
Progression Free Survival ◽  
Study Groups ◽  
Cell Transplant ◽  
Incurable Disease ◽  
Drug Regimens ◽  
Previously Treated ◽  
Additional Agent

Multiple myeloma (MM) is an incurable disease and patients become refractory to the treatment in the course of the disease. Bendamustine-based regimens containing steroids and other agents are among the therapeutic options offered to MM patients. Here, we investigated the safety and the efficacy of bendamustine used in patients with refractory/relapsed MM (RRMM). The patients were treated with bendamustine and steroids (n = 52) or bendamustine, steroids and immunomodulatory agents or proteasome inhibitors (n = 53). Response rates, progression-free survival (PFS), overall survival (OS) and frequency of adverse events were compared between both study groups. Most efficacy measurements were better in patients treated with three-drug regimens: overall response rate (55% versus 37%, p = 0.062), median PFS (9 months versus 4 months, p < 0.001), median OS survival (18 months versus 12 months, p = 0.679). The benefit from combining bendamustine and steroids with an additional agent was found in subgroups previously treated with both lenalidmide and bortezomib, with stem cell transplant and with more than two previous therapy lines. Toxicity was similar in both study groups and bendamustine-based therapies were generally well-tolerated. Our study suggests that bendamustine may be an effective treatment for patients with RRMM. Three-drug regimens containing bendamustine, steroids and novel agents produced better outcomes and had acceptable toxicity. The efficacy of bendamustine combined with steroids was limited.

scholarly journals Updates in the Treatment of Multiple Myeloma

2021 ◽  
Vol 19 (5.5) ◽  
pp. 648-651
Author(s):  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Standard Of Care ◽  
Initial Therapy ◽  
New Drugs ◽  
Cell Transplant ◽  
Nccn Guidelines ◽  
Drug Classes ◽  
High Risk Disease ◽  
Drug Induction ◽  
Relapsed Disease

The treatment of multiple myeloma is marked by many recent advances, but for newly diagnosed patients the standard of care for induction remains the combination of a proteasome inhibitor, immunomodulatory drug, and dexamethasone. The role of a 4-drug induction regimen is still being defined, but can be considered for patients with high-risk disease. For patients who are eligible to undergo stem cell transplant, this approach remains the preferred option, but transplant can be delayed until relapse if patients prefer. In those who are not eligible for transplant, based on impressive data with daratumumab/lenalidomide/dexamethasone, this triplet should be considered as initial therapy. In patients with relapsed disease, it is important to switch treatment to new drug classes; for this, multiple combinations can be recommended. Updated guidelines now include new drugs for refractory disease: selinexor and belantamab mafodotin, both listed as “other regimens” in the NCCN Guidelines, can be considered.

scholarly journals Boosting Immunity against Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1221
Author(s):  
Raquel Lopes ◽  
Bruna Velosa Ferreira ◽  
Joana Caetano ◽  
Filipa Barahona ◽  
Emilie Arnault Carneiro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Complete Response ◽  
Drug Conjugates ◽  
Incurable Disease ◽  
Car T ◽  
Patient’S Outcome ◽  
The Impact

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

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