30 Years of Improved Survival in Non-Transplant-Eligible Newly Diagnosed Multiple Myeloma

Abstract

The treatment of multiple myeloma (MM) has greatly evolved these past few years. Recent advances in therapeutics have largely benefited elderly patients now renamed “non-transplant-eligible” (NTE) patients. Since the 1960s, and for several decades, chemotherapy was the only treatment for MM. Then, the field was marked by the emergence of targeted therapies in the 2000s, such as immunomodulating agents (thalidomide, lenalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), which were the first steps towards an increase in survival. Thereafter, the apparition of monoclonal antibodies (mAbs) was considered a milestone in the treatment of MM for both transplant-eligible and NTE patients. Anti-CD38 mAbs can be safely administered to older patients with an impressive efficacy leading to a never-achieved-before survival rate with the triple association of anti-CD38 mAbs, lenalidomide, and dexamethasone. However, progress is still expected with the introduction in the armamentarium for NTE patients of the most recent innovative immunotherapy-based treatments newly introduced in MM, e.g., CAR-T cells and bispecific antibodies. These “improved versions” of immune-based treatments will probably also benefit NTE patients, although further studies will be needed to better understand their role in this population.

Outcomes of Penta-Refractory Multiple Myeloma Patients Treated with or without BCMA-Directed Therapy

“…Patients with double-hit cytogenetics (more than one high-risk cytogenetic factor) were observed in 26 (41%) patients. The total median LOT till the last office visit/death was eight (3-15) lines, while the median LOT prior onset of penta-RRMM was five (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) lines. Median time from diagnosis of myeloma till the onset of penta-RRMM was 49 (4-176) months, while the median time from onset of penta-RRMM to last office visit/death was 11 (1-67) months.…”

“…The baseline characteristics at T0 are shown in Table 1. The median number of prior LOT (range) before T0 was 5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12); 67 (85%) had a prior stem cell transplant. Interestingly, most patients had high-risk cytogenetics (81%) and extramedullary disease (58%), as highlighted in Table 1.…”

“…Treatment options for MM have grown vastly in the last 25 years with the introduction of several new classes of drugs and a better understanding of the disease pathophysiology, and the development of new therapeutic agents such as proteasome inhibitors (PI), anti-CD38 monoclonal antibodies, and immunomodulatory drugs (IMiDs). In addition, novel agents such as B cell maturation antigen (BCMA)-targeting agents have improved outcomes for patients with MM [2,3].…”

A Kinetically Controlled Bioconjugation Method for the Synthesis of Radioimmunoconjugates and the Development of a Domain Mapping MS-Workflow for Its Characterization

“…The advent of so-called biological therapies, especially based on monoclonal antibodies (mAbs), deeply changed the management of several cancers. , To date, more than a hundred mAbs have been FDA and EMA approved, of which nearly half (42.6%) for cancer treatment . Nevertheless, these drugs still show limitations, mainly due to the emergence of mechanisms of resistance which hinder the long-term survival of cancer patients .…”

Outcomes of Patients with Newly Diagnosed Transplant-Ineligible Multiple Myeloma According to Clinical Trials Enrollment: Experience of a Single Institution

“…However, MM remains a disease associated with high morbidity and mortality [10]. Front-line therapy in non-transplant-eligible (NTE) newly diagnosed MM (NDMM) has significantly evolved in recent years [11]. The armamentarium for this population of patient has evolved from monotherapy to tripe/quadruplet regimens with unprecedented improvements in survival outcomes [10].…”