Characterizing Treatment Patterns in Multiple Myeloma Patients with High-Risk Cytogenetics: A 15-Year-Study
Authors: Venkatesh Priyanka , Rahman Raeef L , Khaliq Aroog , Laharwal Mehak M , Atrash Shebli , McGuirk Joseph P. , Lutfi Forat , Mushtaq Muhammad Umair , Abdallah Al-Ola , Ahmed Nausheen , Mewawalla Prerna , Snyder Jordan , Mahmoudjafari Zahra 
Published: December 2024

Introduction
Treatment options for multiple myeloma (MM) have evolved significantly over the past 5-10 years, with the introduction of several effective new agents and ongoing trials. Despite these improvements, MM remains an incurable disease, particularly for patients with high-risk cytogenetics MM (HRMM). The progressive nature of HRMM often results in multiple relapses, leading to the use of various treatment regimens. We report treatment patterns in the front-line treatment setting, maintenance, and early relapse HRMM in the real-world.
Methods:
We conducted a retrospective study at two medical centers in collaboration with US Myeloma Innovations Research Collaborative (USMIRC) involving HRMM patients (patients). HRMM was defined as deletion 17p, t(14;16), t(4;14), and t(14;20), with or without chromosome 1q gain. We identified 145 patients at two sites with a confirmed diagnosis of HRMM from January 2009 to January 2024 from using electronic health records (EHR). The number and types of agents included in therapy regimens were assessed.
Results:
Out of 145 patients with HRMM who underwent treatment in this cohort, the median age was 61 years (range 33-85). Of these patients, 109 (75%) patients were Caucasian, 83 (57%) patients had IgG isotype, 56 (39%) patients had R-ISS stage III disease, and 22 (15%) patients had extramedullary disease. Double hit myeloma was present in 90 (62%) patients.
Front-line treatment regimens were evaluated in 141 patients. The most prevalent regimen was a triplet regimen in 122 (86.5%) patients, followed by doublet in 9 (6.4%) patients, multi-agent chemotherapy (MAC) in 5 (3.5%) patients, and quadruplet in 5 (3.5%) patients. Overall, proteasome inhibitor (PI)-based therapies were the most frequently utilized at 92.9%, followed by immunomodulator (IMiDs) regimens at 78.7%, chemotherapy (CTX) at 17%, and anti-CD38-Monoclonal antibody (MoAb) at 5%.
Autologous stem cell transplant (ASCT) was utilized in 111 (78.7%) patients, and only one patient (0.7%) received allogeneic stem cell transplant. Maintenance therapy post-transplant was evaluated in 97 patients. The most prevalent approach was monotherapy in 62 (63.9%) patients, followed by doublet in 28 (28.9%) patients, and triplet in 7 (7.2%) patients. Overall, IMiDs-based therapy was the most common at 89.7%, followed by PI-based therapy at 39.1% and anti-CD38 MoAb at 7.2%.
The second line of therapy (LOT) regimens were initiated due to disease progression and assessed in 109 patients. The most prevalent type of regimen was a triplet in 84 (75.7%) patients, followed by salvage transplant in 14 (12.6%) patients, doublets in 6 (5.4%) patients, MAC in 5 (4.5%) patients, and quadruplets in 2 (1.8%) patients. Overall, PI-based therapies were commonly utilized in 57.7% of cases, followed by IMiDs in 63%, anti- CD38-MoAb in 41.4%, CTX in 14.4%, and SLAMF7 MoAb in 0.9%.
The 3rd LOT was evaluated in 96 patients due to disease progression or intolerance in this cohort. The most used type of regimen was the triplet regimen in 60.4% followed by MAC in 14.6%, doublet in 13.5%, monotherapy in 5.2%, quadruplets in 3.1%, and salvage transplant in 3.1%. Overall, PI-based therapies were commonly utilized at 63.5%, followed by IMiDs at 50%, anti-CD38-MoAb at 36.5%, CTX at 29.2% BCMA directed therapies (BDT) at 5.2% and SLAMF7 at MoAb Ab 1%.
Conclusion
Our two-center retrospective study has shown that in the past 15 years, PI and IMiDs are the most used regimen for HRMM in first line and maintenance, as well as second and third lines of treatment. With new approvals and increased utilization, we may observe a rise in the use of anti-CD38 monoclonal antibodies and BDTs in earlier lines of treatment with a dramatic shift of treatment landscape for HRMM.