Pomalidomide vs Carfilzomib for Patients With MM at First Relapse

In a session at the 2022 Great Debates and Updates in Hematologic Malignancies meeting, experts explored pomalidomide vs carfilzomib for patients with multiple myeloma (MM) at first relapse.

Nina Shah, MD, University of California San Francisco, went head-to-head with Rafael Fonseca, MD, Mayo Clinic, Phoenix, Arizona, arguing in favor of pomalidomide for this patient population in the real-world setting.

In support of her argument, Dr Shah discussed the OPTIMISMM study, which assessed bortezomib, pomalidomide, and dexamethasone versus bortezomib and dexamethasone in lenalidomide-exposed relapsed or refractory MM. Patients were randomized in a 1:1 ratio and treated until disease progression or unacceptable toxicity. The primary end point was progression free survival (PFS).

After a median follow-up of 15.9 months, the median PFS in the triplet combination arm was 11.2 months versus 7.1 months for bortezomib and dexamethasone. In addition, the triplet combination results in a 39% reduction in the risk of disease progression and death compared to bortezomib and dexamethasone.

In a subgroup analysis of patients who received 1 prior line of therapy, the triplet combination reduced the risk of disease progression and death by 46%. The median PFS in this population was 20.73 months vs 11.64 months, respectively. These results demonstrate the benefit pomalidomide adds when used with a proteosome inhibitor.

To demonstrate the benefit of pomalidomide with an anti-CD38 monoclonal antibody, Dr Shah discussed the APOLLO study, which assessed subcutaneous daratumumab plus pomalidomide and dexamethasone vs pomalidomide and dexamethasone alone in relapsed or refractory MM. Patients were randomized in a 1:1 ratio and treated until disease progression or unacceptable toxicity. The primary end point was PFS.

Approximately 85% of patients on the APOLLO study had ≥2 prior lines of therapy. At a median follow-up of 16.9 months, the median PFS with daratumumab plus pomalidomide and dexamethasone was 12.4 months compared to 6.9 months with pomalidomide and dexamethasone alone. The triplet combination reduced the risk of disease progression or death by 37% versus pomalidomide and dexamethasone alone.

Although this session is debating pomalidomide vs carfilzomib, Dr Shah did present evidence supporting the use of the 2 drugs in tandem. In the trial setting, use of carfilzomib, pomalidomide, and dexamethasone has been studied multiple times with promising response rates and survival, demonstrating combining these agents can be done safely.

In anticipation of Dr Fonseca’s counterargument, Dr Shah discussed the CANDOR study in which carfilzomib combined with daratumumab and dexamethasone generated a median PFS of 28.6 months vs 15.2 months with carfilzomib and dexamethasone alone. Though this data is promising, it is not representative of the real world, Dr Shah argued.

Aside from the patient outcomes data, there are also other factors to consider when comparing the 2 drugs, including cost and patient time. Carfilzomib is an intravenous drug and is not only expensive but requires a significant amount of the patient’s time. Patients receiving daratumumab, carfilzomib, and dexamethasone must go into the clinical twice a week for 3 out of every 4 weeks for infusion and receive doses on days 1 and 2, 8 and 9, and 15 and 16.

Pomalidomide is an oral drug and patients who are receiving daratumumab, pomalidomide, dexamethasone must go into the clinical every week for 8 weeks and then every other week for 2 weeks and then they come to the clinic once per month to get an injection. In the first year alone, patients receiving daratumumab, pomalidomide, dexamethasone have 23 visits vs 78 visits for patients receiving daratumumab, carfilzomib, and dexamethasone.

“You can show whatever Kaplan-Meier you want, but ultimately patients want to live a quality of life, not just a quantity of life. And this alone is telling you that more of the quantity of life is being taken up by carfilzomib,” stated Dr Shah.

Overall, it comes down to patient preference and from her standpoint, Dr Shah believes pomalidomide is the way to go. “A lot of us are choosing daratumumab plus pomalidomide and dexamethasone because we think that the patients are going to tolerate that better from not only a toxicity standpoint, but from a lifestyle quality of life standpoint,” she concluded.