Frail and/or Older Patients With Multiple Myeloma: ASH 2020 Roundup
At the 62nd ASH Annual Meeting and Exposition, emerging data were presented relevant to the treatment of frail and/or older patients with multiple myeloma. A series of abstracts highlighted the progress that is being made in caring for these groups of patients, in both the newly diagnosed and relapsed/refractory settings.
Our featured expert, S. Vincent Rajkumar, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD, and Dr Rajkumar’s clinical perspectives on these abstracts are presented here.
Edward W. and Betty Knight Scripps Professor of Medicine
“We have made major advances in the treatment of multiple myeloma over the last 15 years. Importantly, many of these advances apply to elderly patients, frail patients, and patients with renal failure, just as they do to patients without these problems.”
The treatment of patients who are elderly, frail, and/or have renal impairment remains a challenge, and outcomes need to improve. If there is a lag in outcomes anywhere, it is likely in these patients, along with the subgroup with high-risk cytogenetics. However, a series of abstracts presented at ASH 2020 highlight that we can, in fact, make progress in these groups, and that progress is already being made.
The report by Dimopoulos and colleagues (abstract 3438) showed that, among heavily pretreated patients and specifically patients with significant renal impairment, treatment with isatuximab in combination with pomalidomide and dexamethasone was associated with better maintenance of quality-of-life parameters compared with treatment with the pomalidomide and dexamethasone doublet alone. There was also a trend toward quality-of-life improvements in patients receiving the triplet, more so than in those receiving the doublet. The authors concluded that these observations align with the findings of the phase 3 ICARIA-MM trial. They are another piece of evidence to add to the larger body of evidence in relapsed populations indicating that a triplet is preferred over a doublet, even in the setting of renal impairment.
Another analysis pertaining to older and frail patients with multiple myeloma was reported in abstract 3215. This was a study of triplet therapy with once-weekly selinexor, bortezomib, and dexamethasone in the BOSTON trial, looking specifically at patients 65 years of age and older vs patients under 65 years of age and frail vs fit patients. A progression-free survival benefit with the once-weekly selinexor, bortezomib, and dexamethasone combination was seen in those aged 65 years and older and in the frail patients. Importantly, the adverse-event profile of this regimen among elderly/frail patients was similar to that of the overall population, with the exception of greater fatigue and pneumonia. So, it is important to remember that these patients may benefit from prophylactic antibiotics to decrease the risk of pneumonia.
Abstract 1381 reported the results of a subgroup analysis of the TOURMALINE-MM4 phase 3 trial, which studied the benefit of single-agent ixazomib as postinduction maintenance therapy in non–transplant-eligible, newly diagnosed patients. Regardless of age or frailty status, ixazomib was associated with significant progression-free survival benefits as maintenance therapy compared with placebo. One of the important things to keep in mind with the addition of ixazomib in elderly patients is that there seems to be an increased risk of peripheral neuropathy. However, when looking at the serious adverse events overall, it is reassuring that there is not much difference between the ixazomib group and the placebo group.
Finally, a retrospective study conducted at the Mayo Clinic evaluated outcomes in patients with newly diagnosed multiple myeloma who were at least 75 years of age at the time of treatment. As reported in abstract 2312, this analysis included almost 400 patients and spanned from 2004 to 2018, reflecting changing practice patterns over that period. Many of these patients were not enrolled in clinical trials. The authors concluded that, even for older patients over age 75 years, being able to receive triplet therapy was linked to improved survival, so this is another analysis that underscores the clear benefits of using triplet therapy.
Overall, these abstracts highlight the major advances in the treatment of multiple myeloma that we have made over the last 15 years. Importantly, many of these advances apply to elderly patients, frail patients, and patients with renal failure, just as they do to patients without these problems. Thus, you do not want to use a less effective regimen simply because a patient is older, is frail, or has renal failure. You might modify the dose for these individuals (eg, rather than using bortezomib, lenalidomide, and dexamethasone [VRd] in elderly and frail patients, we often use VRd-light); however, the goal should be the same: to give the best available therapy.
Using triplet regimens and monoclonal antibodies will help older and frailer patients and should not be avoided based on unfounded fears. In my experience, achieving the advantage of synergy with 3 drugs, even if at reduced dosages, is preferable to giving the full doses of just 2 drugs and withholding the third. This applies to elderly and frail patients, whether they are newly diagnosed or relapsed. For example, the oral proteasome inhibitor ixazomib might be a good option in elderly and frail patients who cannot travel. In addition, monoclonal antibodies should be considered in these individuals because they preserve quality of life and do not add much in the way of toxicity.
Al Saleh AS, Visram A, Parmar H, et al. Treatments and outcomes of newly diagnosed multiple myeloma patients > 75 years old: a retrospective analysis [abstract 2312]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.
Attal M, Richardson PG, Rajkumar SV, et al; ICARIA-MM Study Group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study [published correction appears in Lancet. 2019;394(10214):2072]. Lancet. 2019;394(10214):2096-2107. doi:10.1016/S0140-6736(19)32556-5
Auner HW, Gavriatopoulou M, Delimpasi S, et al. Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: age and frailty subgroup analyses from the phase 3 BOSTON study [abstract 3215]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.
Bringhen S, Pour L, Benjamin R, et al. Progression-free survival (PFS) benefit demonstrated and quality of life (QoL) maintained across age and frailty subgroups with the oral proteasome inhibitor (PI) ixazomib vs placebo as post-induction maintenance therapy in non-transplant newly diagnosed multiple myeloma (NDMM) patients (pts): analysis of the TOURMALINE-MM4 phase 3 trial [abstract 1381]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.
Dimopoulos MA, Campana F, Bury D, et al. Health-related quality of life in heavily pre-treated and renally impaired patients with relapsed/refractory multiple myeloma receiving isatuximab plus pomalidomide and dexamethasone: ICARIA-MM study [abstract 3438]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.
Dimopoulos MA, Špička I, Quach H, et al; TOURMALINE-MM4 Study Group. Ixazomib as postinduction maintenance for patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation: the phase III TOURMALINE-MM4 trial. J Clin Oncol. 2020;38(34):4030-4041.
Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3
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