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Photo of Dr. Aaron Goodman

Are We Ready to Treat Smoldering Myeloma? No!

By Matti McFarlane, MSc Candidate, TMED801 Student

 

On Thursday, November 3rd the TMED first year class had the pleasure of hearing from Dr. Aaron Goodman, MD, from University of California San Diego during Oncology’s guest Medical Grand Rounds. He spoke about the current limitations in treating the blood conditions of smoldering multiple myeloma (SMM) and multiple myeloma, as well as the importance of critically analyzing the current research in this field. Following his presentation, Dr. Goodman kindly met with the TMED students during a facilitated discussion, sharing his thoughts on the importance of patient-centred care, the current directions of cancer research and his experiences as a hematologist/oncologist.

 

In Canada, the 5-year net survival for multiple myeloma patients is only 50% (1) . Dr. Goodman spoke about SMM and multiple myeloma as a paradigm for understanding the design of cancer clinical trials and how to interpret current literature. He began by highlighting the vast improvements in treating multiple myeloma, such as immunomodulatory therapeutics, which have significantly impacted overall patient survival (2). He described SMM as an asymptomatic disease state. More specifically, it is a premalignant clonal plasma cell disorder with a heightened risk of progressing to multiple myeloma (3).

 

Subsequently, Dr. Goodman described the deficits in the most recent diagnostic criteria for SMM and the United States’ guidelines for treatment (4,5). He discussed the challenges associated with the various risk stratification models, which attempt to define the likelihood of disease progression (6). The heterogeneity of these stratification models has led to inconsistent results in clinical trials. Currently, it is very difficult to define which patients are at high risk for progressing to the cancerous disease state. He emphasized that although there are limitations in the current models, the future is bright. Genomic profiling is a promising avenue for identifying patients most at risk for disease progression (7). Dr. Goodman outlined his reservations towards the current treatment guidelines, which recommend treating high-risk SMM patients with the drug lenalidomide before the onset of any clinical symptoms (8). He described perceived issues with hallmark clinical trial study design that support lenalidomide’s recommendation. Specifically, lenalidomide based studies were under powered, used outdated disease classification systems, poor endpoints, ethical concerns etc. Overall, he provided evidence that well-designed clinical trials are warranted to better inform clinical guidelines, treatment, and how clinicians approach care for asymptomatic SMM patients.

 

Continually, Dr. Goodman discussed the research limitations for “active” multiple myeloma, defined as patients with clinical symptoms (i.e., end-organ damage). Specifically, he described: the perceived usefulness of surrogate endpoints frequently used in clinical trials [i.e., Progression Free Survival may not be an appropriate surrogate for Overall Survival], unethical control arms, and poor reporting of post protocol therapy. He contended that many clinical trials inadequately answer clinically relevant questions, such as the benefit of novel (toxic and expensive!) drug protocols on overall patient survival and quality of life. He critiqued the inferior treatment quality in multiple myeloma clinical trial control arms and the lack of gold-standard care for patients following study conclusion (9). Overall, Dr. Goodman raised ethical concerns about how these clinical trials are conducted. Ultimately, some studies may be doing more harm than good for multiple myeloma patients.

 

Following his presentation, Dr. Goodman sat down for an engaging facilitated discussion with TMED students. He spoke to the importance of patient-centred care in his practice, and the role he takes as his patients’ advocate. Additionally, he excitedly engaged our class in a discussion surrounding the promising role of CAR-T cell therapy in cancer therapeutics, which was his inspiration for pursing medicine. He spoke about the unethical practices of multiple myeloma clinical trials and highlighted how they often take advantage of countries where gold-standard treatments are not accessible. This discussion gave insight into the important role translational medicine research can have on patient care, globally. When studies are poorly designed, it leads to less efficacious treatments. For clinicians, the confusing literature can lead to substandard patient care. Dr. Goodman also spoke to the importance of being able to criticize research, a skill the TMED program strives to teach us. Lastly, he gave insight into one of his preferred platforms for sharing academic insights and engaging with like-minded thinkers – Twitter. Find him as @AaronGoodman33, or “Papa Heme”. 

 

I would like to thank Dr. Goodman for generously speaking to the TMED students during his short visit to Kingston. You have certainly instilled in us that we must not be afraid to remind our colleagues that, first and foremost, we must all strive to put patient well-being above all else.

 

References

 

1.         Lee S. Survival statistics for multiple myeloma [Internet]. Canadian Cancer Society. [cited 2022 Nov 9]. Available from: https://cancer.ca/en/cancer-information/cancer-types/multiple-myeloma/p…

2.         Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, et al. Diagnosis and Management of Multiple Myeloma: A Review. JAMA. 2022 Feb 1;327(5):464–77.

3.         Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015 May 14;125(20):3069–75.

4.         Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. The Lancet Oncology. 2014 Nov 1;15(12):e538–48.

5.         NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Multiple Myeloma. Multiple Myeloma. 2013;68.

6.         International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM) | Blood Cancer Journal [Internet]. [cited 2022 Nov 9]. Available from: https://www.nature.com/articles/s41408-020-00366-3

7.         Bustoros M, Sklavenitis-Pistofidis R, Park J, Redd R, Zhitomirsky B, Dunford AJ, et al. Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression. J Clin Oncol. 2020 Jul 20;38(21):2380–9.

8.         Goodman AM, Kim MS, Prasad V. Persistent challenges with treating multiple myeloma early. Blood. 2021 Jan 28;137(4):456–8.

9.         Mohyuddin GR, Koehn K, Sborov D, McClune B, Abdallah AO, Goodman AM, et al. Quality of control groups in randomised trials of multiple myeloma enrolling in the USA: a systematic review. Lancet Haematol. 2021 Apr;8(4):e299–304.