Oncologists' Perspectives and Practices on Minimal Residual Disease Testing in Multiple Myeloma
Authors: Ayoobkhan Fathima Shehnaz , Shatnawi Sara , Shahzad Moazzam , Ur Rehman Aqeeb , Irfan Sohaib , Qureshi Raabia , Khalid Arooq , Chaudhary Sibgha Gull , Anwer Faiz , Ansari Briha , McGuirk Joseph P. , Mohty Mohamad , Ahmed Nausheen , Abdallah Al-Ola , Mushtaq Muhammad Umair 
Published: December 2024

Background: Managing and monitoring patients with multiple myeloma (MM) is crucial. Minimal residual disease (MRD) testing is highly sensitive for evaluating therapy effectiveness. Establishing guidelines for routine MRD testing can improve patient outcomes. We researched oncologists' practice patterns and perspectives on MRD testing to compare opinions based on location and practice setting.

Methods: A global cohort of oncologists participated in an online survey comprising 15 questions. The survey was conducted in collaboration with the International Academy for Clinical Hematology (IACH) and the United States Myeloma Innovations Research Collaborative (USMIRC) from May 2024 to June 2024. Descriptive statistics were used, and proportions were reported. The Chi-square test for categorical variables compared demographic factors associated with MRD testing. Statistical analyses were conducted using Stata version 18,

and significance was defined as p&lt;0.05.

Results:

In a survey of 115 oncologists, 59% (n=67) of respondents were male. Respondents were from the United States (n=42, 36%), Europe (n=39, 34%), South America (13, 11%), Asia (n=10, 9%), Africa (n=9, 8%), and North America other than the US (n=2, 2%). MRD testing was conducted by 44% (n= 51). The only significant positive predictor of the use of MRD testing was specialty (Plasma cell focused practice, 61% vs. Malignant Hematology 57% vs. general Hematology/Oncology 27%, p=0.003). Gender (p=0.671), years in a specialty (p=0.462), practice setting (p=0.544), patients seen per year (p=0.543), and geographic location (p=0.717) did not impact the decision to test. The primary purpose of MRD testing was to discuss the depth of response results with the patients (37%), followed by determining whether to continue treatment (33%), de-escalate treatment (14%), escalate treatment (10%), or discontinue treatment (6%). MRD detection methods utilized were flow cytometry (77%), next-generation sequencing (19%), clonal sequencing (2%), and others(2%). Thresholds for flow cytometry were 10^-5 (41%), 10^-4 (39%), 10^-6 (16%) and not answered (4%). Whole-body imaging for MRD confirmation was used by 72%, 6% preferred whole-body magnetic resonance imaging (MRI), 4% preferred whole-body computed tomography (CT), and 18% did not use imaging.

Following complete remission post-transplant, 31% of participants reported undergoing MRD testing every 6 months, 23% opted for testing every 12 months, 20% responders based on frequency of testing on the patient's response, 16% performed testing every 3-4 months, and 10% did not conduct MRD testing at all. In terms of managing newly diagnosed secretory myeloma cases that tested MRD positive on day 100 post-transplant, the survey results showed that 44% of respondents would initiate consolidation therapy for two additional cycles, 36% preferred to begin maintenance therapy, 12% treated it as relapsed myeloma, and 8% suggested repeating the bone marrow biopsy. Regarding responders, 61% expressed intent to continue lenalidomide of MRD positive and repeat MRD testing to evaluate progress, while 39% stated they would continue lenalidomide until disease progression or intolerance. In cases where MRD testing remained positive after two complete treatment cycles, 50% of the respondents preferred continuing consolidation therapy for two additional cycles before reassessment, 32% favored transitioning to maintenance therapy while continuing MRD monitoring, 14% of the respondents preferred switching to a triplet regimen and to reassess MRD status, and 4% of the respondents opted to switch to maintenance therapy and discontinue MRD monitoring. Among 50 respondents, 54% suggested that the approach would differ based on the patient's transplant eligibility. Reasons for not performing MRD testing included unavailability (27%), lack of impact on treatment (25%), absence of uniformly accepted guidelines (23%), high cost of testing (16%), patient anxiety (2%), unclear benefits (2%), individual decision-making (2%) and others (3%).

Conclusion: For patients with MM, there is considerable variability in MRD testing and management practices based on the MRD results among oncologists globally, underscoring the necessity for further education, outcomes based clinical research and need to develop evidence-based standardized guidelines for use of MRD testing across diverse healthcare environments.