IMS 2025: Quadruplet Regimens Enhance Depth of Response in Multiple Myeloma

In an interview with Pharmacy Times®, Claudio Cerchione, MD, PhD, medical director of hematology at Italy's Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, discussed the evolving role of anti-CD38–based quadruplet regimens in multiple myeloma, particularly for elderly and non-transplant eligible patients. He highlighted his presentation, "Piecing together the evidence: Individualizing anti-CD38 quads in non-transplant patients," which will be shared at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada.

Cerchione emphasized the importance of personalizing treatment based on patient condition, frailty, and comorbidities, noting that these regimens can be used safely even in older patients. He also addressed tolerability, explaining that quadruplet therapy does not significantly increase adverse effects and that deeper responses can improve overall patient well-being and reduce healthcare utilization.

Pharmacy Times: Can you start by introducing yourself?

Claudio Cerchione, MD, PhD: Hello, I am Claudio. I work in the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, in the northern part of Italy, where I lead the clinical and research activities about multiple myeloma.

Pharmacy Times: What key evidence supports the use of anti-CD38–based quadruplet regimens in non-transplant-eligible multiple myeloma patients?

Cerchione: In multiple myeloma, there is an ongoing wonderful revolution, particularly in some settings such as elderly patients and non-transplant-eligible patients. The idea is that the mission is changing, and our efforts are going to achieve the deepest response possible.

In this category of patients, our real endpoint is not anymore just to block the disease or to achieve the best overall response rate and the best progression-free survival. We want to go further. We want to obtain the deepest response, which correlates with MRD negativity. Sustained MRD negativity in the long term could become the cure for multiple myeloma.

At this moment, we have wonderful disease control, and quadruplets help us achieve the best responses possible. Particularly, the integration of isatuximab, a new-generation strong anti-CD38 antibody, together with VRD (bortezomib, lenalidomide, and dexamethasone), is the new standard of care. According to the INNROAD clinical trial, this combination is showing incredible data in terms of depth of response, correlating with very good tolerability.

Even if logistics are not so fantastic for patients, this regimen is showing wonderful quality of life and patient satisfaction. This encourages us to switch from triplet to quadruplet therapy, because what we obtain in the frontline setting at the moment of myeloma diagnosis could be the best approach to correlate with long-term control of patients. We are improving what we use in these patients to obtain the best possible long-term response.

Pharmacy Times: How do you approach individualizing these regimens, and what patient or disease factors most influence treatment selection?

Cerchione: The treatment of multiple myeloma has become more and more personalized. Independently from the division at the moment of a new diagnosis of myeloma in transplant-eligible and non-eligible patients, we also need to correlate the diagnosis with the patient’s condition, frailty score, and comorbidities.

At first, we had a total revolution in our approach to myeloma, switching from chemotherapy to immunotherapy. Now, immunotherapy is becoming more and more personalized. I think there is no preclusion or selection for administering a monoclonal antibody, which has very good tolerability, even in 90-year-old patients.

The idea of using a quadruplet is strictly related to the general status of the patient. If we want to treat the patient as best as possible, we have to give the best opportunity, even if in registration trials the upper age limit was 80 years. I think that if the conditions are good, we can also use it in older patients, and I think we can achieve the best outcomes from that.

Pharmacy Times: What are the main safety or tolerability considerations with anti-CD38 quads, and how can pharmacists help manage them?

Cerchione: At first, we have to consider that the additional monoclonal antibody does not add an impact in terms of tolerability. Data from clinical trials show that tolerability is the same as the triplet alone, without isatuximab. This is an important point.

Moreover, the administration of isatuximab is, at this moment, intravenous, but we know there are solid data about rapid injection. Some trials have shown equivalent results compared with long administration. From the IKEMA and ICARIA clinical trials, we know that an on-body injection is coming, which will make infusion safer, faster, and subcutaneous. This will be another game changer and will increase the possibility for smaller institutions to deliver quadruplet therapy to every patient.

I think the tolerability is really good, and this encourages us to use it in as many patients as possible. Moreover, a patient who achieves a deeper response has better general tolerability, because if we control the disease in a deeper way, the patient goes less to emergency care and less to the general doctor.

In general, there is also an indirect evaluation of the drug regarding side effects not directly related to myeloma. I think this is an important aspect that we can address using quadruplets in the elderly population.