ICER's HTA Report for Multiple Myeloma: New Drugs Clinically Promising, Cost Effectiveness Unclear

A new report released by the Institute for Clinical and Economic Review (ICER) has evaluated the clinical effectiveness, long-term cost-effectiveness, and potential budget impact of treatments for multiple myeloma (MM). Additionally, value-based price benchmarks have been estimated, which consider both the drugs’ long-term cost-effectiveness for patients and the short-term budget impact. The result: too soon to tell.

Three new treatments were approved back-to-back late last year, just prior to the annual meeting of the American Society of Hematology, and they generated a lot of excitement among providers. However, these new options have raised questions of sequencing these agents with existing standard of care and of choosing which treatment would be best for a specific scenario, in addition to the cost associated with it. This would especially difficult in patients who have failed to respond or have relapsed on their previous treatment. A single course of drug treatment for MM in the United States in those who have failed prior treatment ranges from $75,000 to $250,000.

ICER’s analyses focused on evaluating the following treatment combinations as second- or third-line therapy in this subgroup of patients:

• Carfilzomib (Kyprolis) with lenalidomide (Revlimid) and dexamethasone (CFZ+LEN+DEX)
• Ixazomib (Ninlaro) with LEN+DEX (IX+LEN+DEX)
• Elotuzumab (Empliciti) with LEN+DEX (ELO+LEN+DEX)
• Panobinostat (Farydak) with bortezomib (Velcade) and DEX (PAN+BOR+DEX)
• Pomalidomide (Pomalyst) with low-dose DEX (POM+LoDEX)
• Daratumumab (Darzalex) monotherapy (DARA)

The primary considerations when analyzing these combinations included:

• Presence of aggressive or “high risk” disease
• Level and duration of response
• Toxicity exposed to with prior treatment
• Overall functional status and comorbidities due to treatment
• Patient’s choice of enduring the risk of side effects versus benefits of treatment

Thirty eight of 1254 published papers met ICER’s inclusion criteria for this study, which were related to 9 individual studies. ICER considered 6 of these trials:

• ASPIRE
• SIRIUS
• ELOQUENT-2
• TOURMALINE-MM1
• PANORAMA-1
• MM-003

Although overall survival (OS) is the bottom line, MM patients have longer survival trends and only 2 of the 6 trials reported OS data. As for progression-free survival (PFS), except for SIRIUS, all the studies had PFS as the primary trial endpoint. Overall, relative improvements in PFS were similar when stratified based on number of prior lines of therapy.

With respect to toxicity, diarrhea was a primary concern across the 6 studies, responsible for treatment discontinuation. Other significant adverse effects included fatigue, peripheral neuropathy, and thrombocytopenia. Incidence of cardiac effects was also noted with carfilzomib.

The report notes that limitations with the available evidence has reduced ICER’s ability to judge the net health benefits of these regimens. The report points out that using PFS as an endpoint is a controversial issue among clinicians, especially when treating patients aggressive early in their care. The report also notes that there’s a strong divide among clinicians between choosing a “marathon versus a sprint approach” with respect to aggressiveness.

“But perhaps the greatest amount of uncertainty I comparative net health benefits lies in the lack of truly comparative data across trials,” the report states. Expecting progress on this with time, however, the report suggests that CFZ, IX, and ELO, when used in combination with LEN+DEX, would provide an incremental or net health benefit as both second and third-line or subsequent therapies in relapsed/refractory MM.

From the patient perspective, IX and POM are all-oral treatments, while the others are injections or intravenous infusions, and would need a trip to the physician’s office. So IX and POM have potential quality-of-life benefits, the report notes.

When comparing the cost-effectiveness of these treatments, the report found that the incremental costs ranged from a low of approximately $173,000 for CFZ+LEN+DEX to approximately $354,000 for ELO+LEN+DEX versus LEN+DEX. Cost-effectiveness for LEN+DEX was estimated to be $200,000 per quality-adjusted life year (QALY) gained for CFZ+LEN+DEX, $428,000 for ELO+LEN+DEX, and $434,000 for IX+LEN+DEX. While these results varied, all exceeded commonly-cited thresholds of $50,000 to $150,000 per QALY.

While PAN+BOR+DEX was found to be the most cost effective, the report cautions that doubts have been raised about the clinical data on PAN+BOR+DEX.

With respect to the impact of these treatments on the overall economy, the report concludes, “The relatively small patient population for these treatments, our estimate of the potential aggregate costs of treatment with new regimens does not reach the level at which we estimate it would raise a notable concern for affordability across the entire health system.”

The full report can be accessed here.