Salvage Therapy for Amyloidosis in Multiple Myeloma: Agents and Anti-Fibril Therapy

Research is ongoing for the treatment of amyloidosis in multiple myeloma to prove efficacy in decreasing amyloids, according to a presentation at the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting.

Suzanne Lentzsch, MD, PhD, professor of medicine and director of the Multiple Myeloma and Amyloidosis Program at the College of Physicians and Surgeons of Columbia University and at New York Presbyterian Hospital in New York, gave an overview of treating relapsed disease and how a frequent assessment of response as a health care provider is important.

“I usually see my patients every 3 months and make sure they are in a complete remission of at least complete response (CR) or very good partial response (VGPR) with organ response,” Lentzsch said. “And if the patients lose VGPR or stay in VGPR with organ progression, then we consider restart or change in treatments.”

Lentzsch discussed FISH Cytogenetics in amyloid light chain (AL) amyloidosis prognosis, such as translocation, high risk aberrations, and gain of 1q21 and their impact on patients who are treated with bortezomib.

Although she mentioned that there are not many trials in this area of multiple myeloma, some have shown significant data. For example, the phase 3 TOURMALINE-AL1 of ixazomib-dexamethasone versus physician’s choice in relapsed/refractory AL did not meet the primary outcomes, but it did show the ixazomib-dexamethasone hematologic CR rate was higher, as it was the first combination to get approved by the FDA in this area, according to Lentzsch.

Treatment of AL amyloidosis occurs in a hematologic response (monoclonal plasma cells and immunoglobin free light chains) and an organ response (amyloid fibrils and tissue damage), which is being explored in recent studies. However, Lentzsch mentioned how lenalidomide, which is part of the previous anti-amyloid antibodies, has a bad reputation because it can cause cognitive failure in patients. Recent studies have instead used the monoclonal antibody ch11-1F4 mAb, for example, which established a well-tolerated response in the overall median survival time.

Lentzsch reiterated that ixazomib plus dexamethasone improves CR and delays organ deterioration, but the combination failed to achieve the primary endpoint of overall response rate, which makes other options superior, such as autologous stem cell transplant (ASCT). As for other treatments, bendamustine was well-tolerated with 30% VGPR, in addition to venetoclax alone or in different combinations.

“When using Revlimid, do it judiciously, as it can cause high cardiotoxicity,” Lentzsch said. “Anti-amyloid immunotherapy is a tantalizing matter but remains to be proven in decreasing amyloids.”

REFERENCE

Lentzch S. Salvage Therapy for Amyloidosis: Agents and Anti-Fibril Therapy. Presented at: the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting; virtual. September 9, 2021. Accessed September 17, 2021.