The panel moves on to review the profile of a patient with transplant-ineligible, newly diagnosed multiple myeloma managed with dara-Rd on the MAIA trial.
Noopur Raje, MD: I’m going to move on to the next case. Omar, you have an interesting case for us in the transplant-ineligible patient population.
Omar Nadeem, MD: Our patient case No. 2 is of a 72-year-old male who presented to his primary care physician for a routine physical in 2015. Laboratory tests at that time revealed an elevated total protein of 10.4, prompting an SPEP [serum protein electrophoresis], which revealed an IgG [immunoglobin G] kappa monoclonal protein of 2.94 g/dL with reciprocal depressions of quantitative immunoglobulin. His total IgG was 4363 and his kappa free light chains were elevated at 398, with a free light chain ratio of 55. He had a normal creatinine of 0.98. There was no evidence of hypercalcemia, but there was evidence of mild anemia with hemoglobin of 11.1, which had been slowly declining. His beta 2 microglobulin was 2.9 and albumin was normal. His medical history is noted for diabetes, hypertension, coronary disease, for which he’s had prior PCI [percutaneous coronary intervention] and stents, and hypothyroidism. His medications include metformin, glipizide, metoprolol, lisinopril, aspirin, levothyroxine, and gabapentin for some baseline peripheral neuropathy secondary to his diabetes.
He underwent a bone marrow biopsy, which revealed 70% involvement with kappa-restricted plasma cells. FISH [fluorescence in situ hybridization] studies were noted for a translocation 11;14. The patient had a skeletal survey that did not have any evidence of lytic bone disease, and subsequently, a PET [positron emission tomography] scan was also negative for a presence of any lytic bone disease or extramedullary disease. Based on this presentation, with more than 60% plasma cells in the bone marrow and some evolving pattern with his anemia, he was diagnosed with ISS [International Staging System] stage 1, R [Revised]-ISS stage 1, standard risk multiple myeloma, and was deemed transplant-ineligible due to his comorbidities and borderline performance status.
At that time, he had a discussion with his treating team regarding several options available for treatment, which included the regimen of RVd-lite [lenalidomide, bortezomib, and dexamethasone] versus daratumumab, lenalidomide, and dexamethasone on a clinical trial. He was enrolled in the MAIA study and randomized to daratumumab, lenalidomide, dexamethasone in early 2016. The treatment was overall well tolerated, and he achieved a complete response after 6 cycles of therapy. He remains on therapy without any evidence of progression, now in cycle 74. He has had complications from therapy, including some lenalidomide-associated diarrhea, neutropenia, and intermittent upper respiratory infections. As a result, over the years he’s had lenalidomide dose reduced to 5 mg, and daratumumab is now being administered subcutaneously through the transition from IV [intravenous] that occurred during this timeframe. He continues IVIG [intravenous immunoglobulin] for infectious prophylaxis due to those recurrent infections. He is using colestipol for diarrhea that has helped him tolerate the current dose of lenalidomide at 5 mg.
Noopur Raje, MD: This is a great case Omar, thanks for sharing. This is a typical case that we see in our practice. When you start thinking about a transplant-ineligible patient, and you talked about how age is no longer a criteria, it is more the comorbidities. But when we start picking therapies, and we’ve just about finished talking about quadruplet therapy, this is an older, frailer patient population, what are the things that you think about before you pick one drug versus another? Would you use a triplet in this patient? Would you even consider a quadruplet in a transplant-ineligible patient, and how would you define frailty in a patient such as this?
Jacob Laubach, MD, MPP: All critical questions for our field. Regarding the factors that determine choice of therapy, we think about the disease characteristics, which include traditional prognostic factors, beta 2 microglobulin, albumin, and LDH [lactate dehydrogenase], as well as cytogenetic abnormalities. We think about frailty as a patient characteristic, their physical function, kidney function, and the amount of morbidity related to bone events in patients with multiple myeloma is critical. We think about their social circumstances as well. Certain situations, like just getting back and forth to the clinic is quite difficult, and we consider the patient’s preferences about the mode of delivery of their care as well. Fortunately, in this space we have excellent treatment options, 2 regimens, including RVd as well as daratumumab-Rd, that in phase 3 clinical trials have been associated with a survival benefit. So highest level of evidence for both; it can be a challenging decision to choose one versus the other. But a patient who has preexisting peripheral neuropathy, for example, would be a great candidate for daratumumab, lenalidomide, and dexamethasone.
Having been in the field for a while, and remembering some of the early data on how well proteasome inhibitors work in bone involvement, if somebody has significant bone involvement, I’m typically inclined to include a proteasome inhibitor, and bortezomib is a great choice in that context. Those are some of the factors that I consider. There are some patients who are frail where we still would utilize a 2-drug regimen, either lenalidomide and dexamethasone, or perhaps bortezomib and dexamethasone. The question about quadruplet regimens in older patients is being evaluated in ongoing clinical trials, one of which Dr Raje [and others] have been instrumental in leading. That’s a combination of daratumumab plus ixazomib, lenalidomide, and dexamethasone. That’s an ongoing study that will give us important insights into the tolerability of 4-drug therapy in an older patient group, as well as efficacy.
Noopur Raje, MD: Absolutely. Even if they’re transplant ineligible, response rates are important. Whether you are young or old, all of us aim for a deep response. The good news now is that we can get deep responses with the drugs that we have available. Omar, you were able to put this patient on the MAIA trial when they were diagnosed. This patient has done incredibly well on MAIA, and is like a poster child for the trial. Before we talk more about it, Andrew, do you want to update us on the data? We have updated survival data with MAIA, so just walk us through that if possible.
Andrew J. Yee, MD: Sure. Now that the trial has had further follow-up, there was a recent update that looked at the overall survival differences between daratumumab-Rd versus Rd. I believe at the 5-year mark it was 60% versus 50%, the hazard ratio was around 0.7. The takeaway message is that the addition of daratumumab to lenalidomide and dexamethasone improved overall survival. When we think of clinical trials and what we do for our patients, we want to help them live better and longer. It was great to see in the update the improvement in overall survival. Along with that, there weren’t any major changes even though they were on this treatment for this extended time. In terms of any new safety or adverse events, there wasn’t any new signal, so I think it was great to see that.
Noopur Raje, MD: Omar, you described it so well, was it cycle 74? Unbelievable. That’s amazing that the patient was able to continue treatment for that long.
Transcript edited for clarity.