Treatment Options Expanding for Transplant-Ineligible Patients with Myeloma

Autologous stem cell transplant (ASCT) is a key treatment strategy for patients with multiple myeloma, but what about the group of patients who are ineligible for transplant? OncLive, a sister publication of CURE, spoke with Nitya Nathwani, M.D., to find out.

Nathwani, an assistant professor of hematology and hematopoietic cell transplant at City of Hope, explained how patients may be ineligible for transplant for a number of reasons, from age (the average age of diagnosis is 70 years old) to functional status and comorbidities such as dementia, cardiac dysfunction and pulmonary lung issues.

“We need to individualize the treatment of these patients. We want to strive for the best possible response while minimizing toxicity,” he said.

Current standard of care for myeloma is the combination use of Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone — a combination referred to as RVd, which was established based on results from the SWOG S0777 trial.

“That showed significant prolongation in progression-free survival (PFS), as well as overall survival (OS) for the group who received RVd. That study established RVd as the standard of care,” Nathwani said. “However, not all patients are able to tolerate full-dose RVd, so this dose should be reduced as appropriate.”

Depending on their health status, patients may be offered an RVd-“lite” option, which includes all three drugs, but in smaller doses to minimize toxicity. This is a commonly used option for transplant-ineligible patients.

“This regimen was found to be well-tolerated and efficacious and is still awaiting publication. It showed that older patients can still receive a triplet (regimen), which is standard of care, but dose reductions can help them better tolerate the triplet.”

Soon enough, the triplet regimen may not be the only available option for transplant-ineligible patients, as other combinations are currently being explored.

For example, Kyprolis (carfilzomib) plus Revlimid is being looked at, though results are showing that the combination often comes with significant cardiac and pulmonary toxicities.

In February 2018, findings from a Spanish study were published in the New England Journal of Medicine that investigated Velcade, melphalan and prednisone (VMP) in combination with Darzalex.

“This large study showed a clear benefit to the daratumumab-containing arm. The OS data are not mature yet, but there is a significant improvement in PFS and daratumumab was fairly well tolerated,” Nathwani said.

The combination did, however, result in some side effects, with 28 percent of patients on the trial arm experiencing infusion toxicities and 11 percent experiencing grade 3 pneumonia.

A third ongoing study — the MAIA trial – is combining Revlimid and dexamethasone with or without daratumumab for ASCT-ineligible patients. Researchers are awaiting the results of that trial now.

“That study has finished accrual, but we do not have results yet,” Nathwani said.