Strategies for Treating Frail and Transplant-Ineligible Patients With Multiple Myeloma

Shaji Kumar, MD, Mayo Clinic, Rochester, Minnesota, provides insight into strategies for treating frail and transplant-ineligible patients with multiple myeloma (MM). He presented these insights at the 2022 Lymphoma, Leukemia & Myeloma Congress in New York.

Transcript:

Hi, I'm Shaji Kumar. I'm a hematologist at Mayo Clinic in Rochester, Minnesota. I was recently at the Lymphoma, Leukemia and Myeloma Congress in New York City and presented on the approach to treatment of older transplant ineligible patients with newly diagnosed multiple myeloma. As you'll know, the treatment paradigm in myeloma has changed significantly over the past decade and we have many more drugs at our disposal now to treat patients with multiple myeloma.

These drugs are quite effective and predominantly we have been using combinations of proteasome inhibitors, immunomodulating drugs, and the anti-CD38 monoclonal antibodies as part of our initial treatment of newly diagnosed multiple myeloma. Now, the age and the frailty of the patients play an important role in our treatment decision making process, and this is due to a variety of different reasons.

Autologous stem cell transplant remains an integral part of myeloma therapy, but cannot be applied to every patient, particularly the older patients, and those patients who are frail. Assessment of the frailty status and other comorbidities is extremely important when you see patients with multiple myeloma the first time.

The second important reason is that older and more frail patients are more likely to have intolerable side effects to the treatments that we use currently. As a result, we often have to modify the doses of medications we use in these patients, depending on the degree of frailty and the extent of comorbidities that these patients have. There have been a lot of studies that done trying to adjust the doses and starting older and frail patients, on lower doses of medications used in the typical combinations that we use for newly diagnosed myeloma, and this approach seems to work.

An important initial part of the assessment is the assessment of the frailty, in addition to other risk features or risk characteristics of multiple myeloma. Based on this information, currently, we tend to use a three-drug combination, either daratumumab-lenalidomide-dexamethasone or bortezomib-lenalidomide-dexamethasone in the older patients who are not going get a stem cell transplant. The MAIA study demonstrated a significant progression-free survival improvement with the addition of daratumumab, lenalidomide and dexamethasone in this older patient population, and it appears to be fairly well-tolerated with no significant impact on the quality of life.

Similarly, previous phase 3 trials have also shown that the combination of bortezomib-lenalidomide-dexamethasone is effective in this patient group, and also phase 2 studies looking at what we call a VRd-lite regimen using lower doses of bortezomib, lenalidomide and dexamethasone also appear to be equally effective, compared to the standard doses of VRd. So we have the option of these 3 regimens in these patients. In patients with high-risk genetic characteristics, we should try and see if we can [approach] drugs like we do in the younger patients—if it is tolerated. A typical approach would be to start patients on 2 of the drugs or 1 of the drugs with dexamethasone, and then based on how the patients are tolerating them we can add the other drugs over the next 1 or 2 cycles so that patients can get the full benefit of the combination.

Typically in the current practice, we tend to continue patients on these therapies in the disease progression, with bortezomib-lenalidomide-dexamethasone we discontinue the bortezomib after the first [] cycle. Some of these patients have high risk cytogenetics, in which case we continue [] progression. Now in other patients who have significant frailty, one can consider also 2 current combinations, cyclophosphamide dexamethasone as has been done in the FIRST trial and that can also lead to good outcomes. One of the important points to keep in mind is that the frailty status should be reassessed along the course of the treatment as some patients might, once the disease is under control, the frailty indices might significantly improve and I would consider more intense therapies in those patients. They even may become eligible for a monoclonal cell transplant, if other characteristics allow those.

In addition, I think the supportive care management is very important, there are phase 3 studies have shown that antibiotic therapy during the first 2 to 3 cycles can improve outcomes, and this is maybe particularly relevant in patients with multiple myeloma who are frail and older. The impact of comorbidities needs to be taken into consideration. Many of these patients have hypertension and diabetes, which can be made worse with these therapies and that also needs to be monitored very carefully.

Bone health is important, especially in the older patients who often have osteoporosis or osteopenia and a [] acid, or a RANK ligand inhibitor like denosumab should be considered in all patients and after the first year or so, and can certainly be considered every quarter, instead of every month. Overall, I think the use of these newer therapies has allowed these patients to have significant improvement in their survival, and we should continue to optimize the myeloma therapies in supportive in management for these patients.

Source:

Kumar, S. Approaches to Initial Therapy for Patients With Aggressive Lymphoma. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.