Search

Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Immune checkpoint inhibitors upregulate the immune system but can cause immune-related adverse events (irAEs), which may result in treatment delays or discontinuations. Concurrent vaccination is a theoretical risk factor for the increased incidence of irAEs. The use of immunotherapy with inactivated influenza vaccines shows mixed safety data; few published reports involve vaccines beyond the influenza vaccine. OBJECTIVE: To compare the incidence rate of irAEs that require therapeutic intervention in vaccinated patients versus a matched cohort of unvaccinated patients. METHODS: This retrospective, single-center chart review included patients who did and patients who did not receive an inactivated vaccine 30 days before or 60 days after the administration of immune checkpoint inhibitor therapy between January 1, 2015, and July 31, 2019. The vaccinated patients were matched based on age and type of immune checkpoint inhibitor in a 1:2 ratio with patients who were not vaccinated. RESULTS: The study included a total of 213 patients--71 patients in the vaccinated cohort and 142 patients in the unvaccinated cohort. There was no significant difference in the incidence rate of irAEs requiring intervention between the vaccinated and unvaccinated cohorts (22.5% vs 26.8%, respectively; P = .658). There were also no significant differences in treatment delays because of irAEs (11.3% vs 9.2%, respectively; P = .626) or in treatment discontinuations resulting from irAEs (11.3% vs 9.9%, respectively; P = .75). The most common vaccines administered were inactivated influenza vaccines (N = 48), pneumococcal vaccines (PCV13, N = 8; PPSV23, N = 19), and Tdap (N = 8). In all, 49 patients with irAEs required supportive therapy. The most common irAEs were pneumonitis (N = 16) and rash (N = 13). All patients requiring supportive therapy received corticosteroids. CONCLUSION: The results of this study demonstrate that the concurrent administration of inactivated vaccines during immune checkpoint inhibitor therapy does not increase the incidence of irAEs or cause treatment delays and discontinuations. The use of inactivated vaccines in patients receiving checkpoint inhibitor therapy is a safe, guideline-recommended practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tacrolimus is an effective calcineurin inhibitor used for the prevention of graftversus- host disease (GVHD) in patients undergoing allogeneic hematopoietic stem-cell transplant (HSCT). Tacrolimus serum concentrations are monitored after transplant to ensure therapeutic efficacy and reduced adverse drug effects. Many risk factors have been identified in the literature that can alter tacrolimus serum concentrations. OBJECTIVE: To identify patients with target tacrolimus serum concentration levels within 72 hours of conversion from intravenous (IV) to oral dosing, as well as the factors that affect tacrolimus levels after conversion. METHODS: This single-center, retrospective chart review included 236 patients undergoing allogeneic HSCT who received IV tacrolimus in the peri-HSCT period between February 2014 and February 2017 at the University of Kansas Health System. Patients were excluded if they were aged <18 years, received IV tacrolimus outside the peritransplant period, had tacrolimus therapy interrupted for >24 hours, received an allogeneic HSCT not for hematologic malignancy, or received only oral tacrolimus. The study used the institutional protocols for tacrolimus dose adjustments. To reach therapeutic tacrolimus levels, the patient had to be within the target range on 2 consecutive testings at least 24 hours apart. RESULTS: Overall, 63 (26.7%) patients achieved target therapeutic levels within 3 days of conversion from IV to oral dosing of tacrolimus. The median time to target levels after IV to oral tacrolimus conversion was 7 days. The median conversion factor was 2. In a multivariate regression analysis, a 4/8 human leukocyte antigen (HLA)-matched donor significantly (P = .001) increased the time to target tacrolimus levels, and the incidence of diarrhea, although not significant (P = .093), resulted in increased time to reaching target tacrolimus levels. The time to target tacrolimus levels had no effect on the incidence of acute GVHD grade II to grade IV (P = .707) and grade III or IV (P = .348). CONCLUSION: The majority of the patients were not within the target range after the initial conversion from IV to oral tacrolimus. The patients required a median of 7 days to reach the target concentrations, which was increased by having diarrhea or by haploidentical donor cells. However, increased time to target levels did not increase the incidence of acute GVHD after conversion. [ABSTRACT FROM AUTHOR]