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  • decodeMR Team

Complexity and Heterogeneity in Multiple Myeloma: Q & A Session with an Expert

(Focus - India)


In this edition, we turn our focus to multiple myeloma, which accounts for approximately 10% of all hematological malignancies.  

 

The field of multiple myeloma research has witnessed notable advancements like the emergence of various immunotherapies. However, the disease still poses challenges due to its heterogeneity, that influences its diagnosis and treatment. This underscores the importance of continued research and a personalized approach to improving outcomes and enhancing the overall quality of care for affected individuals. 

 

To understand more about the complexities and advancements surrounding multiple myeloma, we have interviewed Dr. Ankur Mittal, a renowned hematologist from India who shares invaluable insights into the distinct characteristics of multiple myeloma, its challenging diagnostic journey, and the evolving landscape of treatment options in India. Dr. Mittal also highlighted the impact of minimal residual disease (MRD) testing on multiple myeloma treatment decisions. 


Dr. Ankur Mittal is a hematologist currently serving at Mohan Dai Oswal Cancer Hospital & Research Foundation, Ludhiana, Punjab, India.



Patients with rheumatoid arthritis generally have bone deformities, and the pain is localized to the joints. However, in multiple myeloma, the patient has diffused generalized pain. As a result, there are no deformities. Fractures were found in patients with multiple myeloma and not rheumatoid arthritis. There is a backache or lower back ache in multiple myeloma, whereas, in rheumatoid arthritis, large or small joints are involved.   

We understand that multiple myeloma is referred to as the "great mimicker" because its symptoms can resemble those of various other diseases [1]. Can you elaborate on some key differences between multiple myeloma symptoms and other diseases it's often confused with? 


Dr. Mittal - If there is a patient with bone metastasis like prostate cancer, their symptoms can mimic the symptoms of multiple myeloma. Bone pain can also mimic other diseases, which sometimes become difficult to diagnose.   


Is it common for multiple myeloma to be initially mistaken for rheumatoid arthritis? 


Dr. Mittal - If we primarily look at the malignant part only, then maybe yes. Otherwise, there are a lot of non-hematological entities that mimic rheumatoid arthritis. In rheumatoid arthritis as well as liver failure, the globulins are high, and there is also anemia. However, in terms of diagnosis, we can differentiate the two.   


What are some of the specific characteristics or nuances in the bone pain experienced by multiple myeloma patients that might distinguish it from the bone pain experienced by rheumatoid arthritis patients? 


Dr. Mittal - Patients with rheumatoid arthritis generally have bone deformities, and the pain is localized to the joints. However, in multiple myeloma, the patient has diffused generalized pain. As a result, there are no deformities. Fractures were found in patients with multiple myeloma and not rheumatoid arthritis. There is a backache or lower back ache in multiple myeloma, whereas, in rheumatoid arthritis, large or small joints are involved.   


In recent years, there has been growing interest in the use of minimal residual disease (MRD) testing in multiple myeloma. However, there is no standard method for MRD detection [2]. Can you provide insights into how MRD testing is being incorporated into the diagnostic process in India and its impact on treatment decisions? 


Dr. Mittal - It is usually done on flow cytometry. NGS and molecular MRDs are yet to be standardized. The MRD process has not been incorporated into the diagnostic process, but it is done during the 100 days post-transplant or when the patient is in remission. However, it is not done too often because even with the biochemical responses, we can plan the treatments, but for those patients who want to get it done, we go ahead and do it for them.  


There are many protease inhibitors and immunomodulatory drugs (IMiDs). We have targeted therapies like Daratumumab. There are many drugs available in India, such as chemotherapy drugs, steroids, and cyclophosphamide. Multiple myeloma patients require continuous therapy.

How can MRD testing impact treatment decisions? 


Dr. Mittal - If the MRD test results are positive, we will probably keep in mind that the disease is quite aggressive, and in maintenance, we should continue with injectables instead of oral medications. Instead of a singlet, we can continue with a doublet. Post-transplant, if the MRD is positive, the chances of relapse are very high. 


Multiple myeloma treatment has evolved significantly in recent years with the introduction of new therapies (3). Can you describe the current landscape of treatment options available in India, including both traditional and novel approaches? 


Dr. Mittal - There are many protease inhibitors and immunomodulatory drugs (IMiDs). We have targeted therapies like Daratumumab. There are many drugs available in India, such as chemotherapy drugs, steroids, and cyclophosphamide. Multiple myeloma patients require continuous therapy.

 

It is difficult to make the patient understand that multiple myeloma requires continuous therapy and monitoring. Generally, once the patient is asymptomatic or symptom-free, they discontinue the treatment.   

Chemotherapy has traditionally been a mainstay of multiple myeloma treatment. Can you discuss any emerging therapies or targeted treatments that serve as alternatives or complements to chemotherapy in India? 


Dr. Mittal - CAR T-cell is an example, along with Ixazomib and Daratumumab targeted therapy. There are also biallelic antibodies. They are good alternatives to chemotherapy because response rates are good, and there are fewer side effects.   


Precision medicine is becoming increasingly important in cancer treatment. Are there any personalized or precision medicine approaches being utilized in the treatment of multiple myeloma patients? 


Dr. Mittal - I do not think so. From cytogenetic reports, if the risk is high, we plan for doublets in the maintenance, and we consider transplants. Otherwise, I don’t think there is any difference. 


What challenges do you encounter when treating multiple myeloma patients, and what steps or initiatives can be taken to address and overcome these challenges? 


Dr. Mittal - It is difficult to make the patient understand that multiple myeloma requires continuous therapy and monitoring. Generally, once the patient is asymptomatic or symptom-free, they discontinue the treatment.   


Awareness and patient counselling about the disease is how we have to go ahead. The family should also support the patient.   


We understand that treatment resistance is one of the challenges encountered while treating multiple myeloma patients [3]. Could you provide insights into the treatment and management strategies for patients with relapsed/refractory multiple myeloma? 


Dr. Mittal - We have around 9 to 10 drugs or maybe even more than that, and we can do the permutation and combination for the triplet or the quadruplet that we will be giving to the patients. We also have to look into the timings of the relapse rates and the financials that the patients have, and accordingly, we can plan the treatment. It depends on how the drug has been received by the patient and the functional status of the patient.   


What message or advice would you like to convey to multiple myeloma patients and their caregivers to help them effectively manage their condition? 


Dr. Mittal - They should be aware of the disease and how to go about it. Then only they will be able to pick it up. 


Thank you for sharing your valuable insights 


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