Omar Nadeem, MD from Dana-Farber Cancer Institute speaks about HORIZON (OP-106): Melflufen Plus Dexamethasone (dex) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM)-Analysis of Adverse Events Related to Hospitalizations.
Context:
RRMM pts are a very ill group due to signs of illness, comorbidities, medication side effects, and age-related fragility (Chim et al. Leukemia. 2018;32:252). Adverse events (AEs) that impair their quality of life and decrease medication compliance are also encountered by Pts; hematologic AEs are frequent. Inpatient facilities are also required for AE management and are a significant cost driver, with costs increasing per AE episode (highest for hematologic AEs; Felber et al. ASH 2019. Abs. 4725). In addition, a real-world study showed that >50 percent of pts with hematologic AEs need hospital readmission after initial care (Yeaw et al. ISPOR 2020. Abs. PCN78). The data reported to date comes from real-world evidence, with minimal clinical trial results.
A first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells is melphalan flufenamide (melflufen). Melflufen plus dex demonstrated clinically relevant efficacy and safety profile in the pivotal phase 2 HORIZON study (OP-106; NCT02963493), consisting primarily of clinically manageable hematologic AEs in pts with heavily pretreated RRMMM (Richardson et al. EHA 2020. Abs EP945). In a clinical trial, this study helps to further elucidate the healthcare resource usage of pts with melfulfen-treated RRMM by assessing the effect of AEs on HORIZON hospitalizations.
Methodology:
Melflufen and dex were treated with Pts with RRMM that had received about 2 lines of prior therapy, including an IMiD and a proteasome inhibitor, and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody, as stated (Richardson et al. EHA 2020. Abs EP945). Data for particular AEs potentially linked to study drugs (melflufen and/or dex; TRAEs) requiring hospitalizations of >24 h were compared with all possible TRAEs and recorded irrespective of hospitalization with >1 event within each preferred word. AEs were listed by the treating physician as TRAE if identified as linked or likely connected to either study medication.
Outcomes:
157 pts were reported at the data cutoff date (14 Jan 2020) and received around 1 dose of study treatment; 35 (22%) were hospitalized due to TRAE. The median age of Pts hospitalized due to TRAEs was 63 y (range, 43-84); 31 percent had stage 3 disease of the International Staging System; 49 percent had high-risk cytogenetics; and 77 percent had triple-class refractory MM.
Thrombocytopenia (57 percent), neutropenia (53 percent), and anemia were the most common grade 3/4 treatment-emergent AEs (TEAEs) in the total population (N=157) (43 percent ). In 49 percent of pts, severe AEs occurred, most commonly pneumonia (9 percent) and febrile neutropenia (5 percent ). 118 (3.2 percent) of all 3713 TEAEs contributed to hospitalization. 58 (2.2 percent) of 2688 TRAEs resulted in hospitalization. TRAEs with pneumonia and febrile neutropenia resulted in the majority of hospitalizations, with 11 cases (78.6% of TRAEs with pneumonia; 0.41% of all TRAEs) and 10 events (83.3% of TRAEs with febrile neutropenia; 0.37% of all TRAEs), respectively (Table). Grade 3/4 hospitalized hematologic TRAEs included thrombocytopenia (9 hospitalizations; 1.4% of TRAEs for thrombocytopenia; 0.33% of all TRAEs) and neutropenia (2 hospitalizations; 0.3 percent of neutropenia TRAEs; 0.07 percent of all TRAEs). Except for 2 cases, all TRAEs that resulted in hospitalization were grade 3/4. (1 pyrexia [grade 1]; 1 pneumonia [grade 2]). It was uncertain if the hospitalization was >24 h for 3 out of 9 thrombocytopenia events and 1 out of 2 neutropenia events, but they were included in the current study.
The Conclusion:
Most TRAEs could be handled without the need for hospitalization within this highly pre-treated pt community. Hematologic AEs were prevalent but, ultimately, led to few hospitalizations. While 11 cases (78.6%) of pneumonia TRAEs required hospitalization, these events account for just 0.41% of all TRAEs, and infections are usually predicted in advanced RRMMs (Blimark et al. Plasma Cell Disorders. 2015;100:107). The utilization of inpatient care is a significant driver of RRMM’s economic burden and has been shown to be heavily used in communities with less pretreatment than HORIZON (Yeaw et al. ISPOR 2020. Abs. PCN7; Felber et al. ASH 2019. Abs. 4725). The findings of this study show that inpatient facilities for TRAEs with melflufen plus dex have restricted use. To validate the findings presented from this study, further analyses of real-world data on melflufen are warranted.