In a bold leap of scientific innovation, researchers have recently unveiled the findings of a pioneering Phase I study examining the effects of a new combination therapy for patients with relapsed and refractory Multiple Myeloma (MM). The study, published in the ‘Clinical Lymphoma, Myeloma & Leukemia’ journal, has set a new pathway for future treatments leveraging existing drugs for a disease known for its aggressive and resilient nature.

Repurposing Common Medications to Fight Multiple Myeloma

The study, cited with DOI: 10.1016/j.clml.2024.01.002, is led by a distinguished team of researchers from the Mayo Clinic, including notables Ibrahim I. Alodhaibi, Sikander S. Ailawadhi, Gabriel P. Burbano, Patrick J. O’Brien, Francis K. Buadi, Suzanne S. Hayman, Shaji K. Kumar, and Wilson I. Gonsalves (electronic address: gonsalves.wilson@mayo.edu). It saw metformin, traditionally used as a complex I inhibitor in the treatment of diabetes, and nelfinavir, a GLUT4 inhibitor used to treat HIV/AIDs, being repurposed in conjunction with bortezomib—a chemotherapy medication commonly used in MM treatment.

Study Design and Outcomes

Initiated on January 6th, 2024, the study was structured around a 3 + 3 dose escalation design and incorporated 3 dose levels for up to a maximum of 6 (21-day) cycles. Patients took metformin and nelfinavir for 14 of the 21 days, while subcutaneous bortezomib was administered on days 1, 8, and 15. The nine patients who participated were noted to have a median age of 65 and had received a median of 7 prior lines of therapy.

The primary objective was to determine the maximal tolerated dose, whereas the secondary aim focused on safety and overall response rate (ORR). Despite not achieving an ORR, the researchers observed some signs of potential benefit. One patient, for instance, experienced a stable disease (SD) response, which enabled the stabilization of their condition until they could access another novel therapy on a clinical trial. This finding, while not as fruitful as hoped, signals a minor victory in a realm where every small step is crucial.

The Impact of Findings on the Future of MM Treatment

Although this open-label Phase I study did not meet the lofty expectations set forth, the findings signify progress. The novelty of this combined therapeutic approach holds immense promise, as it dives into uncharted territories where traditional treatments have fallen short.

Reference Insights and Continuing Education

As the medical community continues to digest these results, additional research and clinical trials will undoubtedly emerge, capitalizing on the insights gleaned from this initial endeavor. For those who wish to delve deeper into the study’s methodology and results, here are some valuable references to consider:

1. Alodhaibi, I. I., Ailawadhi, S. S., Burbano, G. P., O’Brien, P. J., Buadi, F. K., Hayman, S. S., … Gonsalves, W. I. (2024). An Open-Label Phase I Study of Metformin and Nelfinavir in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma. Clinical Lymphoma, Myeloma & Leukemia, S2152-2669(24)00019-3, 10.1016/j.clml.2024.01.002.

2. Moreau, P., Richardson, P. G., Cavo, M., Orlowski, R. Z., San Miguel, J. F., Palumbo, A., & Harousseau, J. L. (2012). Proteasome inhibitors in multiple myeloma: 10 years later. Blood, 120(5), 947-959.

3. Rajkumar, S. V., Kumar, S. (2016). Multiple Myeloma: Diagnosis and Treatment. Mayo Clinic Proceedings, 91(1), 101–119.

4. Chng, W. J., Dispenzieri, A., Chim, C. S., Fonseca, R., Goldschmidt, H., Lentzsch, S., … Rajkumar, S. V. (2014). IMWG consensus on risk stratification in multiple myeloma. Leukemia, 28(2), 269-277.

5. Kumar, S. K., Rajkumar, S. V., Dispenzieri, A., Lacy, M. Q., Hayman, S. R., Buadi, F. K., … Gertz, M. A. (2021). Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. Journal of Clinical Oncology, 33(26), 2863-2869.

Advocacy and Support for MM Patients

Patients suffering from MM and their families can look toward these findings as a beacon of hope, even if the road to a cure remains arduous. This study emphasizes the importance of drug repurposing strategies in oncology—a creative and cost-effective approach that may accelerate the discovery of promising treatments for various malignancies including MM.

Keywords

1. Multiple Myeloma Treatment
2. Bortezomib Therapy
3. Drug Repurposing Oncology
4. Metformin Nelfinavir Bortezomib
5. Phase I Clinical Trials MM

Moving Forward

The dedication and perseverance of the research team from the Mayo Clinic in the quest to combat Multiple Myeloma must be commended, as must the courage of the patients who participate in such trials. They are the unsung heroes in the relentless pursuit of a cure, and though this study did not yield the breakthrough many hoped for, it is a testament to the resilience and ingenuity inherent in the medical research community. It is a stepping stone upon which future successes will be built.