Novel Agents as Main Drivers for Continued Improvement in Survival in Multiple Myeloma

Abstract

(1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied 1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980–1990, 1991–2000, 2001–2010 and 2011–2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980–1990, 37.4 months in 1991–2000, 61.8 months in 2001–2010 and 103.6 months in 2011–2020 (p < 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months (p < 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up

“…In MM, the average lifespan is nearly ten years [3]. Cytogenetic abnormalities play an important role in the prognosis of the disease and are assessed at the time of diagnosis [4].…”

Immune Therapies in AL Amyloidosis—A Glimpse to the Future

“…Notwithstanding recently uncovered differences in underlying disease biology [5,6], treatment approaches successful in MM have effectively translated to treatment of AL amyloidosis. Thus, mirroring improvements in MM survival over the last decades with the introduction of novel therapeutic agents [7][8][9][10][11], progress has also been made in the treatment of AL amyloidosis [12]. Nevertheless, the prognosis of many patients, especially frail patients who are less able to tolerate the toxicity of effective therapies, remains dismal [13,14].…”

“…The aforementioned improvements in survival in both MM and AL amyloidosis in the last decades have largely been the result of widespread adoption of so-called novel agents, including proteasome inhibitors, immunomodulatory agents [10,19], and the anti-CD38 monoclonal antibody daratumumab, the first immunotherapy to gain the approval of the Food and Drug Administration (FDA) for treatment of MM [20] and subsequently AL amyloidosis [21]. More recently, the spectrum of immunotherapeutic agents (i.e., therapies that stimulate the host immune system to target cancerous cells) in MM has widened to include antibody-drug conjugates (ADCs), bispecific antibodies (BSAs), and chimeric antigen receptor T cells (CART).…”

Role of flow cytometric measurable residual disease assessment in multiple myeloma

“…Advances in diagnostics and risk stratification, and more importantly the increasing availability of new therapies, have improved long-term outcomes for patients with MM [4]. Current treatment regimens using immunomodulatory drugs and second-and third-generation proteasome inhibitors in combination with autologous stem cell transplantation (auto-SCT) are achieving complete responses (CR) in up to 70-80% of patients [5][6][7].…”