Novel Treatment Strategies in R/R Multiple Myeloma

Ravi Vij, MD, MBA:For patients who are elderly and have multiple myeloma that has relapsed, the challenges are more marked than for those who are otherwise in good health. The choice of regimen has to be tailored to the frailty of the patient. One of the things that we are realizing is important in patients who are older is a proper geriatric assessment. Cursory assessments like performance status using the KPS [Karnofsky Performance Status] scale, the ECOG [Eastern Cooperative Oncology Group] scale, are not sufficient sometimes to get a true sense of what patients can or cannot tolerate. In regard to patients who are having comorbidities and are frail, we need to be sure that we reduce the dose of agents that we use conventionally in patients who are younger and healthier. They often cannot tolerate the full doses of their drugs.

Also, we need to tailor our treatments. Not every patient, honestly, who is older and frailer, will tolerate a 3-drug regimen. In some patients, we have to go back to using 2-drug regimens to balance the toxicity with the efficacy. In older patients, we are often willing to give up some efficacy for better tolerability. The older patients are the ones who often will require drugs to be given serially rather than concurrently. We know that the older patients have a more challenging situation to overcome compared with the younger population that we treat.

We are fortunate in multiple myeloma that we have had a good 2 decades. We have had several new classes of drugs become available to patients that were not available in the past. What is even more exciting is that we have certainly not finished with the discoveries in multiple myeloma. There are a lot of new compounds in clinical trials that look promising.

In regard to the BCMA-directed therapies, the B-cell maturation antigen is a molecule present mainly on plasma cells, so it offers the chance for developing targeted therapies. The BCMA antigen has been targeted using CAR [chimeric antigen receptor] T cells, which have been the subject of great excitement and have results that are unparalleled to any other modality in such a refractory population. But also, BCMA is being targeted using other strategies like antibody drug conjugates, bispecific molecules, and these offer more ready, off-the-shelf access for patients.

Patients also should look forward to the approval of other new classes of drugs in multiple myeloma. Venetoclax, a drug that is already marketed for some leukemias and lymphoma seems, to be active in multiple myeloma, especially for patients who have a translocation involving (11;14). There are other drugs in development, including a drug called selinexor, which is an XPO1 inhibitor that offers patients, even with penta-refractory disease, responses that are approaching about 20% to 25% as a single agent. So I think this is certainly a disease where there is a lot of optimism about treatments in development, and outcomes for patients will improve even further.

Transcript edited for clarity.

Case: 75-Year-Old Man With Symptomatic R/R Multiple Myeloma

January 2015

• A 75-year-old man was diagnosed with multiple myeloma; R-ISS stage I
• PMH: hypertension; coronary artery disease post stent placement
• Patient was treated with lenalidomide + dexamethasone for 9 months; transplant-ineligible due to age and performance status
• Patient achieved a VGPR, discontinued treatment thereafter due to patient request

September 2018

• On routine follow-up 3 years later, patient presents with new-onset back pain and generalized fatigue
• Imaging: multiple new lytic lesions with compression fractures
• Laboratory results:
  • Hb, 10.7 g/dL
  • Ca²⁺, 9.3 mg/dL
  • Creatinine, 1.1 mg/dL
  • M-protein, 3.2 g/dL
• Cytogenetics/FISH: del (17p) discovered at relapse
• ECOG PS: 2