Analysis Finds Daratumumab Combo Offers Better PFS Than Bortezomib Combo in Newly Diagnosed MM

When multiple therapeutic combinations are listed in the National Comprehensive Cancer Network guidelines, how do clinicians select the best one for patients?

An analysis presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) offered some answers to this question in newly diagnosed multiple myeloma (MM). Investigators used data from a pair of key trials to compare results for daratumumab with lenalidomide (Revlimid) and dexamethasone (DRd) vs bortezomib (Velcade) with lenalidomide and dexamethasone (VRd).¹

Using trial data from the MAIA and SWOG S0777 trials, investigators drilled down into individual patient-level data to create an indirect treatment comparison of DRd (MAIA) and VRd (SWOG S0777). The analysis adjusted for the trials’ differences in inclusion criteria and baseline patient characteristics. According to the abstract, age 65 or older served as a proxy for transplant ineligible status, because the SWOG S0777 trial enrolled a mix of transplant ineligible and transplant-not-intended patients. The median age of patients evaluated was 63 years.

According to the study authors, propensity score (PS) reweighting allowed for balancing of the different trial populations age, sex, cancer stage, ECOG performance status, and other factors. After this reweighting, the authors wrote, “an anchored indirect comparison was performed wherein within-trial progression-free survival (PFS) hazard ratios (HRs) for DRd vs Rd and VRd vs Rd were estimated,” and these evaluations were then used to make indirect comparison about PFS between DRd and VRd.

In total, 727 patients from the MAIA trial and 198 from the SWOG S0777 trial were eligible for the analysis. Results showed the following:

• Adjusted PFS HRs for DRd vs Rd was 0.53 (95% CI, 0.41–0.68; P < .0001) and VRd vs Rd was 0.88 (0.63–1.23; P = .46).
• The adjusted Rd-anchored indirect comparison found the PFS HR for DRd vs VRd was 0.60 (0.39–0.90; P = .02).

Study authors concluded that in this indirect comparison, PFSwas significantly longer for DRd relative to VRd. Lacking a head-to-head trial comparing the 2 regimens, they concluded, “ the present study may help to inform treatment selection in transplant ineligible patients with newly diagnosed multiple myeloma.”

At-home Subcutaneous Daratumumab Evaluated

A poster session at ASCO featured details of an open-label, single-arm trial that will evaluate the implementation of home administration of subcutaneous daratumumab. As the authors stated in their abstract, MM has a high burden for patients and their caregivers, requiring frequent visits to hospitals or clinics, and new care delivery models are needed to alleviate patient burden and improve quality of life.²

“Chemotherapy at home remains uncommon in the US, though models for its use exist globally,” they wrote. “In these models, home-based chemotherapy is safe, preferred by patients, and can be administered at lower cost.”

The trial (NCT05511428) will study home-based subcutaneous daratumumab and hyaluronidase-fihj, sold as Darzalex Faspro, for patients with MM. The study authors hypothesize that this program will reduce patient treatment and financial burden and improve quality of life. Using the Cancer Therapy Satisfaction Questionnaire (CTSQ), investigators will evaluate 20 responses when patients receive at home care, as compared with standard of care.

Secondary outcomes will include assessing adherence, quality of life as measured the EORTC QLQ-30 scale, financial burden as measured by the COST survey, safety of home administration, and barriers to home administration. Investigators will also conduct semi-structured interviews to evaluate patient experience with home administration of chemotherapy.

Eligible patients must have a diagnosis of MM, and be in the monthly phase of daratumumab treatment, either as monotherapy or in combination with other agents. The study will last for 8 cycles of daratumumab—2 cycles in the infusion center, 4 cycles at home, and 2 cycles in the infusion center. Labs will be performed at a local lab or at home.

Of note, the investigators write, on at-home daratumumab days, the drug will be mixed and packaged by the study pharmacy, “then delivered at room temperature to the patient’s home by our home infusion courier,” where it will administered by a nurse, after the patient takes premedications 1-3 hours prior to the nurse’s arrival.

Both studies are funded by Janssen.

References

1. Durie BG, Kumar S, Ammann EM et al. Adjusted indirect treatment comparison of progression-free survival (PFS) associated with DRd and VRd based on MAIA and SWOG S0777 individual patient-level data. J Clin Oncol. 2023;41 (suppl 16):abstr 8037. doi:10.1200/JCO.2023.41.16_suppl.8037
2. Binder AF, Martinez-Outschoorn UE, Wilde L, et al. Open label single arm study to assess the implementation of home based daratumumab administration in patients being treated for multiple myeloma. J Clin Oncol. 2023;41(suppl 16);abstr TPS1609. doi:10.1200/JCO.2023.41.16_suppl.TPS1609