Multiple myeloma (MM) predominantly affects older adults, and first-line (1L) management—particularly for transplant-ineligible patients—requires careful consideration of efficacy, safety, and quality of life. A substantial proportion of newly diagnosed patients are older than 75 years and often present with comorbidities or varying degrees of frailty, making individualized treatment planning essential. Real-world evidence also suggests attrition across subsequent lines of therapy, underscoring the importance of thoughtful initial treatment decisions.
The frontline landscape for transplant-ineligible MM has evolved alongside greater consideration of immunotherapy-based approaches, including CD38-targeting strategies, within combination regimens. CD38 is highly expressed on MM cells and plays a role in immune regulation within the bone marrow microenvironment. Targeting this pathway may contribute to immune-mediated tumor cell killing while modulating immunosuppressive cell populations, potentially shaping early anti-tumor immune responses.
In routine clinical practice, many transplant-ineligible patients are managed with continuous, lower-intensity combination approaches rather than fixed-duration therapy, depending on patient characteristics and care goals. Decisions around treatment selection, sequencing, duration, and monitoring are often guided by patient fitness, tolerability, and evolving priorities over time. Frail patients may be more susceptible to toxicity and treatment discontinuation, highlighting the importance of dose or schedule adjustments and ongoing reassessment to support treatment continuity and quality of life.
In your practice, how do frailty or geriatric assessments influence first-line treatment selection and ongoing management for transplant-ineligible patients with multiple myeloma? When considering continuous therapy, how do long-term goals—such as preserving quality of life and functional independence—factor into your treatment decisions alongside efficacy?
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ALIREZA MIRMIRAN1wI favor doublet therapy in elderly and frail patients. I typically do limited duration therapy and not continuous therapy in the geriatric population. -
Joshua Strauss1moWe don't perform formal geriatric assessments but for patients with significant comorbidity and impaired performance status, we will tailor treatments for tolerability. Quads are still the gold standard but may need to de-escalate to triplets if needed. Dara-Rev-Dex is still an excellent regimen for non-transplant eligible patients and I have many patients doing well on this for some time. Quality if life is critical and I often make dose or regimen adjustments to account for this, especially for patients who are already in deep remissions.
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Holavanahall Keshavaprasad1moMost patients with multiple myeloma are elderly. They do have various comorbid conditions, both primary de novo, and secondary to the myeloma and sometimes treatment. The treatment regimens for myeloma are mostly not chemotherapy based. However the drugs do cause various side effects such as peripheral neuropathy, thrombocytopenia, anemia, herpes zoster, thrombosis. These may cause additional morbidity, and sequela such as bleeding, infections, falls and so on. Since myeloma is incurable, we will treat aggressively in elderly patients with quadruple therapy, but use triple or dual therapy for less frequent patients, with a view to maximize quality of life, reasonable efficacy and minimize side effects.
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Venu Madhav Konala1moIn a community clinic setting, frailty and geriatric assessment play a key role in guiding first-line treatment for transplant-ineligible patients with Multiple Myeloma. Because many patients are older and have comorbidities, use simple frailty measures—such as age, comorbidity burden, and functional status—to determine whether a patient can tolerate more intensive regimens. Some patients may start with quadruplet therapy, while others begin with triplet therapy such as daratumumab, lenalidomide, and dexamethasone based on results from the MAIA trial. Immunotherapy-based approaches targeting CD38 are commonly incorporated when appropriate because they can provide strong disease control. Treatment is typically given continuously, but maintain a low threshold to adjust doses or schedules to minimize toxicity. The overall goal is to balance efficacy with preservation of quality of life and functional independence, particularly in frail patients.
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Kumar Abhishek1moFrailty does influence the choice of frontline treatment. I use CD38 containing quad regimen for most patients with a decent performance status. For those who are transplant eligible I use DaraRVd and for others who are transplant ineligible, I use IsaRVd based on the respective approvals and trials. I do not formally assess frailty by questionnaire but by eyeball test and get up and go test. For patient who do not get transplant, I continue CD 38 and IMid maintenance and drop Velcade. My goal is to prevent relapse. Since the visits and treatment could be once a month in maintenance, the burden of treatment is low. I also use the minimal effective dose of Rev to reduce the long term chronic AEs.
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Elan Gorshein1moIn older/more frail patients, especially over the age of 80, I tend to prefer dara/rev/dex (MAIA trial) with a low threshold to adjust or discontinue dexamethasone after 2-3 cycles. I do consider quad based therapy as well and ultimately depends on the above factors. With continuous/maintenance therapy stopping dara and continuing rev monotherapy may be an option, especially if standard risk
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Prabhsimranjot Singh1moGeriatric assessment are important to help if considering de-escalating therapy ; but if otherwise fit irrespective of age would use quad therapy
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Karlos Oregel1moDepends, I think patients who are fit I would still push for a quad therapy otherwise there is data for Dara-len- low dose dex in this population
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KARL D'SILVA1moI prefer using a triplet regimen consisting of Dara SQ with Revlimid and Dex. this regimen is excllent in tranpslant ineliglbe patients
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Cynthia Scott1monot in my area
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SACHINKUMAR PANCHAL1moUsing Triple Regimen helps, replace with cyclophosphamide if history of BC
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Rahat Sheikh1moI always use a triplet regimen that always helps.
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ALIREZA MIRMIRAN1moI favor the use of triplets in these patients
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Matt Manico1moThe quad of D-RVD is a standard for transplant eligible patients and those with a good PS. With frail patients, response rates are very reasonable with a dara containing triplet. I usually have a discussion with frail patients on their goals and the efficacy vs tolerability trade-off
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KUMAR ABHISHEK2moyes frailty does influence the choice of frontline treatment. I use CD38 containing quad regimen for most patients with a decent performance status. For those who are transplant eligible I use DaraRVd and for others who are transplant ineligible, I use IsaRVd based on the respective approvals and trials. I do not formally assess frailty by questionnaire but by eyeball test and get up and go test. For patient who do not get transplant, I continue CD 38 and IMid maintenance and drop Velcade. My goal is to prevent relapse. Since the visits and treatment could be once a month in maintenance, the burden of treatment is low. I also use the minimal effective dose of Rev to reduce the long term chronic AEs.
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ELIE FAHED2moFor older/frail patients I favor triplets(MAIA regimen) instead of Quads. I try to continuer Rev/Dara maintenance beyond 2 years but that really depends on tolerance. For very old/very frail I stop one of the two drugs and I am very aggressive in lowering the Rev dose
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ALEXANDER BARSOUK2moMore likely to use triplet regimen DRd for frail patients to minimize neuropathy. Also sometimes replace revlimid for cyclophosphamide if patient has history of blood clots
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Mayer Gorbaty2moIn the older elderly (eg >80) and very frail I would hold bortez so as to minimize neurotoxicity but proceed with dara/len dex to try and get the best myeloma control. The patient is monitored closely and dose adjustments are frequent. Otherwise for younger elderly and the nonfrail I would try a quadruplet. Some form of maintenance is generally done- often with dara/len. Quality of life and functional independence are essential parameters to be followed.
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David Vesole3moIn frail and elderly patients with limited lifespans independent of their myeloma diagnosis, quality of life is the key. Yes, the recent IMROZ trial of quadruplet therapy included approximately 30% frail and elderly, who apparently tolerated the regimen. I, for one, do not administer bortezomib in this population-I cannot imagine the negative impact of peripheral neuropathy (still over 50% any PN) to a population who is at risk for falls. Yes, the bortezomib is discontinued after 6 cycles but that is more than enough time to develop PN. Even if one gives the bortezomib weekly, the incidence of PN is still 20-25%. Therefore, i give this population a triplet. Even with the triplet, one must be liberal in dose adjusting the lenalidomide and dexamethasone to modify for toxicities. Until we have data to support discontinuation of therapies (coming in the future) based upon MRD negative, the standard of care is continuous treatment of one or more of the induction regimen agents.
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Sumit Sawhney3mogenerally treat to a maximal response ,pts with high fraility index and comorbid conditions where the life expectancy is limited due to co morbid conditions usedoublets to keep disease under control and give quality of life not looking for remissions