Tafasitamab 200mg powder for solution for infusion vials

ObjectivesNovel interventions (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tafasitamab-lenalidomide [Tafa-L], polatuzumab-rituximab-bendamustine [pola-BR]) improve clinical outcomes in second-line (2 L) treatment of transplant-ineligible patients with early relapse or refractory (R/R) diffuse large B cell lymphoma (DLBCL). The costs vary depending on the respective treatment regimen and the treatment duration, difficult comparability in reimbursement decisions. The objective was to analyze the health economic impacts of novel 2 L interventions and conventional immunochemotherapies (bendamustine-rituximab [BR], rituximab-gemcitabine-oxaliplatin [R-GemOx]) from a German healthcare payer's perspective as a function of treatment duration.MethodsAn economic model was developed to compare treatment costs of 2 L interventions depending on the treatment duration. Treatment duration was measured by progression-free survival (PFS), identified based on a systematic review. Total and average costs were calculated over 5 years to evaluate incremental costs at median PFS for each intervention.ResultsAverage costs per month at median PFS ranged from €2846 (95% CI: 5067-1641) to €40 535 (95% CI: 91180-N/A) for BR and liso-cel, respectively. Incremental costs at the lowest median PFS (R-GemOx: 5.3 months) revealed -€664, €5560, €11 817, €53 145, and €67 745 for BR, Tafa-L, pola-BR, axi-cel, and liso-cel as compared to R-GemOx, respectively.ConclusionsAnalyses uncovered a variation of incremental costs of 2 L transplant-ineligible DLBCL interventions as a function of time leading to amortization of high-priced interventions.

Abstract licence: CC BY-NC

AbstractFollicular lymphoma with progression of disease within 24 months (POD24) is associated with poor prognosis and represents clinical challenges. Therefore, we performed a systematic review and pooled analysis of patients with POD24. Twenty-one trials involving 1242 participants were included, assessing the overall response rate (ORR), complete response (CR), duration of response, and progression-free survival. In some trials, we compared pooled response rates between POD24 and non-POD24 populations with the same treatment regimen. Four trials evaluated chimeric antigen receptor (CAR) T-cell therapy in patients with POD24. Pooled analysis showed an ORR of 91.2% (95% confidence interval [CI], 83.7-98.7) with significant heterogeneity (P = .0414; I2 = 68.61%) and a CR of 75.7% (95% CI, 55.1-96.4) with significant heterogeneity (P< .0001; I2 = 93.99%). The specific response rates for different bispecific antibodies in POD24 were pooled analysis, the ORR was 81.6% (95% CI, 75.9-87.3) with no heterogeneity (P = .6958; I2 = 0%), and the CR was 65.7% (95% CI, 57.1-74.3) with moderate heterogeneity (P = .2148; I2 = 34.99%). For anti-CD19 antibody-drug conjugates (ADCs)/monoclonal antibodies (mAbs), the ORR and CR rate for loncastuximab plus rituximab and tafasitamab plus R2 (lenalidomide + rituximab) were 100% and 79.3%, and 87.5% and 43.2%, respectively. Phosphatidylinositol 3-kinase inhibitors and anti-CD20 mAb-containing regimens were also analyzed in pooled analyses. Our results demonstrated that anti-CD19 CAR T-cell therapy achieved the highest CR rate. Additionally, bispecific antibodies, anti-CD19 ADCs/mAbs, and the combination of lenalidomide with obinutuzumab or rituximab also exhibited excellent efficacy. Notably, lenalidomide plus obinutuzumab showed superior efficacy compared with R2.

Abstract licence: CC BY-NC-ND

Relapsed/refractory follicular lymphoma (R/R FL) remains a clinically challenging condition, with progressively declining benefit across consecutive lines of therapy. While anti-Cluster of Differentiation 20 (CD20) antibodies remain the therapeutic backbone, the optimal targeted or immune-based partner remains undefined. A systematic review and network meta-analysis (NMA) of 5 phase III and 1 phase II trials (2500 patients) evaluated seven anti-CD20-based combination strategies. Primary end-points were overall survival (OS) and progression-free survival (PFS); secondary end-points included objective response rate (ORR) and grade ≥3 adverse events. Treatments were ranked using surface under the cumulative ranking (SUCRA) values. Immune-activating strategies ranked highest across efficacy end-points. Epcoritamab plus rituximab (R2) achieved the top SUCRA rankings for OS, PFS and ORR, while tafasitamab plus R2 consistently ranked second, with a better safety profile. R2 alone showed intermediate efficacy and good tolerability, whereas zanubrutinib plus anti-CD20 demonstrated modest efficacy with lower toxicity. Bortezomib and copanlisib-based combinations ranked lowest for efficacy, with phosphoinositide 3-kinase (PI3K) inhibitor-based regimens showing the least favourable benefit-risk profile. Anti-CD20 monotherapy was the safest but least effective option. This NMA indicates that immune-centric, anti-CD20-anchored combinations represent the most effective chemotherapy-free strategies for R/R FL. Combinations incorporating anti-CD19 or CD20/CD3 bispecific antibodies appear to offer deeper disease control, particularly in high-risk and rituximab-refractory disease.

Abstract licence: CC BY

Tafasitamab plus lenalidomide (TAFA + LEN) received accelerated US Food and Drug Administration approval and conditional European Medicines Agency approval for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for autologous stem cell transplant. This study investigates the relative efficacy of TAFA + LEN versus comparator treatments. Matching-adjusted indirect comparisons (MAICs) of TAFA + LEN were performed using data from L-MIND, and comparator studies assessing rituximab-based combination therapies, including polatuzumab vedotin + bendamustine + rituximab (POLA + BR) bendamustine + rituximab (BR), and gemcitabine + oxaliplatin + rituximab (R-GEMOX) to provide relative efficacy estimates for overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and complete response rate (CRR). Patient-level data from L-MIND were weighted to match reported distributions of clinically validated prognostic factors and effect modifiers in comparator trials. MAIC results versus multiple BR studies were pooled using meta-analysis. MAICs were feasible versus POLA + BR and BR. Compared to POLA + BR, TAFA + LEN was associated with significantly longer DOR [hazard ratio (HR) 0.34 (95% CI 0.12, 0.98); p = 0.045]. Due to concerns about the proportional hazard assumption for OS and PFS, separate HRs were estimated before and after 4 months of follow-up. OS after 4 months, was significantly greater for TAFA + LEN versus POLA + BR [HR 0.41 (95% CI 0.19, 0.90); p = 0.026]. Compared with BR, TAFA + LEN was associated with significantly improved OS [GO29365 comparator trial: HR 0.39 (95% CI 0.18, 0.82); p = 0.014], PFS (pooled data: HR 0.39 (95% CI 0.29, 0.53); p < 0.001], DOR [pooled data: HR 0.35 (95% CI 0.25, 0.50); p < 0.001], and CRR [pooled data: odds ratio 2.43 (95% CI 1.33, 4.41); p = 0.004]. In MAIC analyses, treatment with TAFA + LEN for R/R DLBCL provided better OS and PFS outcomes than standard treatment regimens. Validation from large, randomized, phase 3 clinical trials is required to confirm these results. Tafasitamab in combination with lenalidomide has been recently approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma. There are no clinical trials to directly compare the outcomes of tafasitamab + lenalidomide against other treatments for diffuse large B-cell lymphoma. Matching-adjusted indirect comparisons allow an estimate of the relative efficacy of treatments to be derived in the absence of head-to-head comparisons from clinical trials. Matching-adjusted indirect comparisons analyses utilizing data from previously published clinical trials were conducted to compare the combination of tafasitamab + lenalidomide against 3 standard treatments for relapsed or refractory diffuse large B-cell lymphoma: polatuzumab vedotin + bendamustine + rituximab, bendamustine + rituximab, and rituximab + gemcitabine + oxaliplatin. Compared to those treated with polatuzumab vedotin + bendamustine + rituximab, patients treated with TAFA + LEN maintained their response to treatment for longer and are more likely to experience long-term survival. When compared to those treated with bendamustine + rituximab, patients treated with TAFA + LEN had increased survival, a higher level of response, and maintained their response to treatment for longer. Overall, the findings suggest that treatment with TAFA + LEN for R/R DLBCL is likely to result in significantly better outcomes compared with standard rituximab-based treatments.

Abstract licence: CC BY-NC 4.0

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Newly approved treatments for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and large B-cell lymphoma (LBCL) include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR) and tafasitamab plus lenalidomide (tafa-len). The effectiveness of pola-BR and tafa-len in clinical practice has been evaluated in recent real-world studies (Hamadani et al, ASH 2022; Qualls et al, ASH 2022). Epcoritamab, an off-the-shelf subcutaneous CD3xCD20 T-cell–engaging, bispecific antibody that redirects CD3+ T cells to eliminate malignant CD20+ B cells, has demonstrated deep and durable responses with manageable safety across R/R LBCL patient populations, including those with difficult-to-treat LBCL. In the absence of head-to-head trials, there is a need to assess the comparative efficacy of these therapies. Aims: To compare the efficacy of epcoritamab vs CAR T, pola-based regimens, and tafa-based regimens (including variations of pola-BR and tafa-len) in R/R DLBCL and LBCL. Methods: This study compared individual patient data from the EPCORE™ NHL-1 trial (NCT03625037; Jan 2022 cutoff) and multiple US academic and community clinical practices in the COTA electronic health records database (2010–2022), including adult patients with R/R DLBCL and LBCL treated with CAR T, pola-based, and tafa-based regimens with ≥2 prior lines of therapy (LOTs). Inverse probability of treatment weighting was used to create balanced cohorts on key demographic and clinical characteristics. Outcomes were compared across balanced cohorts: patients treated with epcoritamab vs those treated with other novel therapies (ie, CAR T-naive LBCL patients in EPCORE NHL-1 vs CAR T patients, and all DLBCL patients from EPCORE NHL-1 vs patients treated with pola-based and tafa-based regimens in the COTA database). Overall response rate (ORR) and complete response (CR) rate were compared using weighted logistic models; progression-free survival (PFS) and overall survival (OS) were compared using weighted Cox proportional-hazard models. Results: A total of 96 CAR T-naive LBCL patients were included in the epcoritamab cohort vs 55 in the CAR T cohort (axicabtagene ciloleucel, 60%; tisagenlecleucel, 14.6%), and 139 DLBCL patients in the epcoritamab cohort vs 37 receiving pola-based regimen and 20 receiving tafa-based regimen. Cohorts were balanced on several factors including but not limited to prior CAR T exposure (in epcoritamab vs pola-based and tafa-based regimens), number of prior LOTs, and refractoriness to last LOT. For epcoritamab vs CAR T, CR rate was 38.9% vs 36.5%. For epcoritamab vs pola-based and tafa-based regimens, CR rate was 38.9% vs 10.7% and 11.2%, respectively. Adjusted odds ratio (95% CI) for CR for epcoritamab vs CAR T was 1.14 (0.79, 1.64; P=0.472); for epcoritamab vs pola-based regimens was 3.60 (2.04, 6.37; P<0.0001); and for epcoritamab vs tafa-based regimens was 3.48 (2.01, 6.01; P<0.0001). Adjusted hazard ratio (95% CI) for OS for epcoritamab vs CAR T was 1.08 (0.70, 1.69; P=0.724); for epcoritamab vs pola-based regimens was 0.44 (0.32, 0.62; P<0.0001); and for epcoritamab vs tafa-based regimens was 0.53 (0.38, 0.75; P=0.0003). Other clinical outcomes are summarized in the Table. Summary/Conclusion: Epcoritamab provides significantly better efficacy vs pola-based and tafa-based regimens, with no significant difference vs CAR T, in patients with R/R DLBCL and LBCL who received ≥2 prior LOTs. These findings are subject to limitations consistent with comparative analyses conducted outside of a randomized clinical trial.Keywords: Real world data, Survival, Bispecific, Clinical outcome

Abstract licence: CC BY-NC-ND 4.0

BackgroundApproximately 40% of patients with high-risk diffuse large B-cell lymphoma (DLBCL) are not cured with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone). We aimed to investigate the addition of tafasitamab (an Fc-enhanced anti-CD19 monoclonal antibody) and lenalidomide to R-CHOP (tafa-len-R-CHOP) in patients with high-risk aggressive B-cell lymphomas.MethodsfrontMIND is a phase 3, randomised, double-blind, placebo-controlled study conducted at 298 centres in North America, South America, Europe, and the Asia-Pacific region. Patients aged 18-80 years with previously untreated, high-intermediate-risk or high-risk DLBCL or high-grade B-cell lymphoma (HGBL) were randomly allocated (1:1), stratified by International Prognostic Index (IPI) or age-adjusted IPI and geographical region, to receive six 21-day cycles of standard R-CHOP (rituximab 375 mg/m2 intravenous on day 1, cyclophosphamide 750 mg/m2 intravenous on day 1, doxorubicin 50 mg/m2 intravenous on day 1, vincristine 1·4 mg/m2 [maximum 2 mg] intravenous on day 1, and prednisone or prednisolone 100 mg/day orally on days 1-5); patients in the tafa-len-R-CHOP group additionally received tafasitamab (12 mg/kg intravenous on days 1, 8, and 15) plus lenalidomide (25 mg/day orally on days 1-10), while those in the R-CHOP group received matching placebos. The primary endpoint was investigator-assessed progression-free survival (defined as time from randomisation to disease progression or death from any cause), analysed in the intention-to-treat population; safety was included as a secondary endpoint among all patients who received at least one dose of study treatment. The trial is registered with ClinicalTrials.gov (NCT04824092) and EUDRA-CT (2020-002990-84) and is active but no longer enrolling.FindingsBetween May 11, 2021, and March 2, 2023, 1229 patients were screened, among whom 899 were randomly allocated: 448 (50%) to the tafa-len-R-CHOP group and 451 (50%) to the R-CHOP group. At the time of primary analysis (median follow-up 35·2 months [95% CI 35·0-35·4]), progression-free survival was improved in the tafa-len-R-CHOP group versus the R-CHOP group (hazard ratio [HR] 0·75 [95% CI 0·59-0·96]; p=0·0194), with 2-year progression-free survival rates of 71·1% (66·3-75·4) with tafa-len-R-CHOP versus 62·9% (57·9-67·5) with R-CHOP. Interim HR for overall survival was 0·85 (0·63-1·14). The overall rate of grade 3 or higher treatment-emergent adverse events was higher with tafa-len-R-CHOP (384 [87%] of 443) than with R-CHOP (340 [76%] of 447). Additionally, a higher rate of fatal treatment-emergent adverse events was observed with tafa-len-R-CHOP (26 [6%]) than with R-CHOP (17 [4%]). However, the number of overall deaths in the study was lower with tafa-len-R-CHOP than with R-CHOP (82 [19%] vs 97 [22%]). Based on disposition data, rates of premature discontinuation of all study drugs were similar in the tafa-len-R-CHOP group (71 [16%] of 443) and R-CHOP group (66 [15%] of 447).InterpretationProgression-free survival was significantly improved with tafa-len-R-CHOP versus R-CHOP; however, the safety profile indicated increases in adverse events, including treatment-emergent adverse events leading to death, with the addition of tafasitamab and lenalidomide. Overall survival data are immature; follow-up is ongoing. Further analyses, including of circulating tumor DNA, will help to assess whether deeper molecular responses are contributing to the progression-free survival benefit observed with tafa-len-R-CHOP. Tafa-len-R-CHOP might represent a potential new first-line treatment for patients with high-risk DLBCL or HGBL.FundingIncyte Corporation.

Abstract licence: CC BY