Time-dependent cost comparison and health economic impact analysis of second-line interventions for transplant-ineligible patients with relapsed or refractory diffuse large B cell lymphoma.

OBJECTIVES: Novel 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. METHODS: An 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. RESULTS: Average 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. CONCLUSIONS: Analyses 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.

Tafasitamab for the treatment of patients with diffuse large B-cell lymphoma.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) require additional treatments, especially those not eligible or not responding to high dose cytotoxic chemotherapy and stem cell transplantation. Over the last few years, several new treatments have been developed and approved for these patients, among them of particular relevance are those targeting CD19. Tafasitamab is a humanized monoclonal antibody targeting CD19, composed of a modified fragment crystallizable (Fc) region engineered with higher affinity for Fc gamma receptors (FcγR) receptors, leading to increased cytotoxicity through natural killer cells and macrophages (antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated phagocytosis). In this product review, we will discuss its mechanism of action, safety profile and efficacy results from clinical trials that led to its approval in combination with lenalidomide for patients with R/R DLBCL ineligible for high-dose chemotherapy and autologous transplantation.

Preclinical study of CD19 detection methods post tafasitamab treatment.

Introduction: Several CD19 targeted antibody-based therapeutics are currently available for patients with diffuse large B-cell lymphoma (DLBCL), including the Fc-modified antibody immunotherapy tafasitamab. This therapeutic landscape warrants the evaluation of potential sequencing approaches. Prior to a subsequent CD19-targeted therapy, CD19 expression on tafasitamab-treated patient biopsy samples may be assessed. However, no standardized methods for its detection are currently available. In this context, selecting a tafasitamab-competing CD19 detection antibody for immunohistochemistry (IHC) or flow cytometry (FC) may lead to misinterpreting epitope masking by tafasitamab as antigen loss or downregulation. Methods: We analyzed a comprehensive panel of commercially available CD19 detection antibody clones for IHC and FC using competition assays on tafasitamab pre-treated cell lines. To remove bound tafasitamab from the cell surface, an acidic dissociation protocol was used. Antibody affinities for CD19 were measured using Surface Plasmon Resonance (SPR) or Bio-Layer Interferometry (BLI). Results: While CD19 was successfully detected on tafasitamab pre-treated samples using all 7 tested IHC antibody clones, all 8 tested FC antibody clones were confirmed to compete with tafasitamab. An acidic dissociation was demonstrated essential to circumvent CD19 masking by tafasitamab and avoid false negative FC results. Discussion: The current study highlights the importance of selecting appropriate CD19 detection tools and techniques for correct interpretation of CD19 expression. The findings presented herein can serve as a guideline to investigators and may help navigate treatment strategies in the clinical setting.

Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma.

Background: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. Methods: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Results: Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. Conclusion: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo.

Targeted Treatment of Adults with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Tafasitamab in Context.

The outcomes of Relapsed/Refractory (R/R) Diffuse Large B-cell lymphoma have been historically poor. The recent development of several novel therapies including CD19 directed agents has improved the prognosis of this disease significantly. Chimeric antigen receptor (CAR) T-cell therapy has drastically changed the treatment of R/R DLBCL, but it is still associated with significant barriers and limited access. Tafasitamab (an anti-CD19 engineered monoclonal antibody), in addition to lenalidomide, has shown significant efficacy with exceptionally durable responses in patients with R/R DLBCL who are ineligible for autologous stem cell transplantation (ASCT). Tafasitamab-lenalidomide and certain other therapies (ie, antibody-drug conjugates and bispecific antibodies) are important treatment options for patients who are ineligible for CAR-T due to co-morbidities or lack of access, and patients with rapid progression of disease who are unable to wait for manufacturing of CAR-T. This review will thus discuss currently approved and recently studied targeted treatment options for patients with R/R DLBCL with an emphasis on CAR-T alternative options, particularly Tafasitamab-lenalidomide.

RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma.

RE-MIND2 (NCT04697160) compared patient outcomes from the L-MIND (NCT02399085) trial of tafasitamab+lenalidomide with those of patients treated with other therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are autologous stem cell transplant ineligible. We present outcomes data for three pre-specified treatments not assessed in the primary analysis. Data were retrospectively collected from sites in North America, Europe, and the Asia Pacific region. Patients were aged ≥18 years with histologically confirmed DLBCL and received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients enrolled in the observational and L-MIND cohorts were matched using propensity score-based 1:1 nearest-neighbor matching, balanced for six covariates. Tafasitamab+lenalidomide was compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR), rituximab+lenalidomide (R2), and CD19-chimeric antigen receptor T-cell (CAR-T) therapies. The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and progression-free survival. From 200 sites, 3,454 patients were enrolled in the observational cohort. Strictly matched patient pairs consisted of tafasitamab+lenalidomide versus pola-BR (n = 24 pairs), versus R2 (n = 33 pairs), and versus CAR-T therapies (n = 37 pairs). A significant OS benefit was observed with tafasitamab+lenalidomide versus pola-BR (HR: 0.441; p = 0.034) and R2 (HR: 0.435; p = 0.012). Comparable OS was observed in tafasitamab+lenalidomide and CAR-T cohorts (HR: 0.953, p = 0.892). Tafasitamab+lenalidomide appeared to improve survival outcomes versus pola-BR and R2, and comparable outcomes were observed versus CAR-T. Although based on limited patient numbers, these data may help to contextualize emerging therapies for R/R DLBCL. CLINICAL TRIAL REGISTRATION: NCT04697160 (January 6, 2021).

Clinical Treatment Guidelines for Tafasitamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 24% of new cases of B-cell non-Hodgkin lymphoma in the US each year. Up to 50% of patients relapse or are refractory (R/R) to the standard first-line treatment option, R-CHOP. The anti-CD19 monoclonal antibody tafasitamab, in combination with lenalidomide (LEN), is an NCCN preferred regimen for transplant-ineligible patients with R/R DLBCL and received accelerated approval in the US (July 2020) and conditional marketing authorization in Europe (August 2021) and other countries, based on data from the L-MIND study. The recommended dose of tafasitamab is 12 mg/kg by intravenous infusion, administered in combination with LEN 25 mg for 12 cycles, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. Tafasitamab + LEN is associated with durable responses in patients with R/R DLBCL. The majority of clinically significant treatment-associated adverse events are attributable to LEN and can be managed with dose modification and supportive therapy. We provide guidelines for the management of patients with R/R DLBCL treated with tafasitamab and LEN in routine clinical practice, including elderly patients and those with renal and hepatic impairment, and advice regarding patient education as part of a comprehensive patient engagement plan. Our recommendations include LEN administration at a reduced dose if required in patients unable to tolerate the recommended dose. No dose modification is required for tafasitamab in special patient populations.

Tafasitamab and lenalidomide for relapsed/refractory diffuse large B-cell lymphoma in a patient on chronic intermittent hemodialysis.

INTRODUCTION: Tafasitamab is an anti-CD19 monoclonal antibody indicated for the treatment of relapsed/refractory diffuse large B-cell lymphoma to be given in combination with lenalidomide. Experiences with tafasitamab in the setting of hemodialysis are limited and the efficacy and safety of this agent in this setting are unknown. CASE REPORT: We describe a patient with relapsed/refractory diffuse large B-cell lymphoma with hemodialysis-dependent end-stage renal disease who successfully received tafasitamab/lenalidomide. MANAGEMENT AND OUTCOME: Tafasitamab and reduced dose lenalidomide were initiated for relapsed diffuse large B-cell lymphoma. Tafasitamab was administered on non-dialysis days. Follow-up imaging for disease response assessment demonstrated a complete response. Therapy was well tolerated; the only major toxicity experienced was grade 4 neutropenia that resolved with dose adjustment to lenalidomide. Over a year from initiating therapy, the patient remains in a complete response. DISCUSSION/CONCLUSION: The combination of tafasitamab and dose-reduced lenalidomide produced a complete response in the treatment of relapsed/refractory diffuse large B-cell lymphoma in the setting of chronic intermittent hemodialysis.

Targeting CD19 for diffuse large B cell lymphoma in the era of CARs: Other modes of transportation.

CD19 is nearly ubiquitously expressed on B-lymphocytes and in B-cell malignancies. Although CD19-directed CAR T cells have greatly improved outcomes in B-cell malignancies, there are significant limitations with this therapy. CD19 can also be effectively targeted by other drug classes, such as monoclonal antibodies, antibody-drug conjugates, and bispecific T cell engagers or antibodies. However, the optimal patient selection and sequencing of these novel therapies has not yet been established. In this review, we discuss the utilization of CD19 as a target for the treatment of DLBCL, focusing on tafasitamab, loncastuximab tesirine, and blinatumomab. We provide a comprehensive review of the pivotal clinical trials, discussing the strength and limitations of the data for each agent. We explore the emerging evidence that CD19 expression is retained following exposure to these agents and that patients can be successfully re-challenged with anti-CD19 therapies of a different drug class upon disease relapse post-CAR T cells. Finally, we discuss how these drugs potentially fit into the most current treatment paradigm for DLBCL.

Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma: New Approved Options.

Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL) have refractory disease or relapse after the first line of treatment. Until relatively recently, the prognosis of patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. In recent years, several novel therapies have been approved that provide more effective options than conventional chemotherapy and that have manageable toxicity profiles. CAR-T cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of the phase 3 ZUMA-7 and TRANSFORM clinical trials. This review addresses the role of CAR-T therapy and autologous stem cell transplantation in the treatment of these patients and other approved options for patients who are not candidates for transplant, such as the combinations of polatuzumab vedotin with bendamustine and rituximab, and tafasitamab with lenalidomide.

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

Tafasitamab mediates killing of B-cell non-Hodgkin's lymphoma in combination with γδ T cell or allogeneic NK cell therapy.

Tafasitamab is an Fc-modified monoclonal antibody that binds to CD19, a cell-surface antigen that is broadly expressed on various types of B-cell non-Hodgkin's lymphoma (NHL). Antibody-dependent cellular cytotoxicity (ADCC), a key mode of action of tafasitamab, is mediated through the binding of tafasitamab's Fc region to FcγRIIIa receptors on immune effector cells and results in antitumor activity. Despite the proven clinical activity of tafasitamab in combination with lenalidomide in the treatment of diffuse large B-cell lymphoma (DLBCL), a higher number of immune cells in cancer patients may improve the activity of tafasitamab. Here, we characterized two ex vivo-expanded FcγRIIIa receptor-expressing cell types-γδ T and MG4101 natural killer (NK) cells-as effector cells for tafasitamab in vitro, and found that in the presence of these cells tafasitamab was able to induce ADCC against a range of NHL cell lines and patient-derived cells. We also explored the concept of effector cell supplementation during tafasitamab treatment in vivo by coadministering MG4101 NK cells in Raji and Ramos xenograft models of NHL. Combination treatment of tafasitamab and allogeneic MG4101 NK cells in these models demonstrated a survival benefit compared with tafasitamab or MG4101 monotherapy (Raji: 1.7- to 1.9-fold increase in lifespan; Ramos: 2.0- to 4.1-fold increase in lifespan). In conclusion, adoptive cell transfer of ex vivo-expanded allogeneic NK or autologous γδ T cells in combination with tafasitamab treatment may potentially be a promising novel approach to increase the number of immune effector cells and enhance the antitumor effect of tafasitamab.

Real-world data in drug development strategies for orphan drugs: Tafasitamab in B-cell lymphoma, a case study for an approval based on a single-arm combination trial.

Tafasitamab (TAF) plus lenalidomide (LEN) is a novel treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) who are not eligible for autologous stem cell transplantation. The initial US/EU approvals for TAF represent precedents because this is the first time that approval of a novel combination therapy was granted based on a pivotal single-arm trial (SAT). Matching real-world data (RWD) helped to disentangle the contribution of individual agents. In this review, we present the TAF development strategy, the prospective incorporation of RWD within the clinical development plan, the corresponding regulatory hurdles of this strategy, and the prior regulatory actions for other cancer drugs that previously incorporated RWD and propensity score matching in EU and US regulatory submissions. We also outline how RWD could further advance and impact orphan drug development.

Newly approved anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Objective: This article summarizes the background, clinical trials, and place in therapy for the first two anti-CD19 monoclonal antibodies that have been recently FDA approved for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Summary: Treatment options are limited for patients that have relapsed after or are ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T-cell therapy. Recent novel therapy approvals have started to change management strategies and outcomes for these patients. Two examples of recent FDA approvals are tafasitamab and loncastuximab tesirine, which represent the first anti-CD19 targeting monoclonal antibodies for patients with R/R DLBCL. Tafasitamab was granted accelerated approval in combination with lenalidomide for adult patients with R/R DLBCL after one or more lines of therapy based on the phase 2, L-MIND trial. Loncastuximab tesirine was granted accelerated approval for adult patients with R/R DLBCL after two or more lines of therapy based on the phase 2, LOTIS-2 trial. The place in therapy and sequencing of these agents can present a challenge to prescribers especially in regards to patients being evaluated for CD19 targeting CAR T-cell therapy. Conclusion: Tafasitamab and loncastuximab tesirine are options for use in patients with R/R DLBCL and are welcome additions to the limited therapy options for these patients. Further data is needed to elucidate sequencing and the impact these agents may have on CAR T-cell therapy. Ongoing clinical trials are studying these agents in the upfront setting in combination with other chemoimmunotherapy agents which may further expand treatment options for patients with B-cell lymphomas.

Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report.

The histologic transformation (HT) of Waldenström macroglobulinemia (WM) into diffuse large-cell lymphoma is an uncommon but poor-prognostic event for which there is no standard therapy. Knowledge of this entity is mainly derived from largely retrospective studies, which report abysmal average survival rates even with the utilization of first-line chemoimmunotherapy and especially in patients who meet the high-risk criteria based on prognostic indices used for WM. We present the case of a 75-year-old man with high-risk, transformed WM who was ineligible for standard chemoimmunotherapy (due to pancytopenia and multiple comorbidities) and was consequently treated with tafasitabmab, an anti-CD19 monoclonal antibody plus lenalidomide. Tafasitamab plus lenalidomide (TAF/LEN) is a recently approved therapy for relapsed or refractory de novo diffuse large-cell lymphoma (DLCL) but has not been previously studied in transformed low-grade lymphomas or WM. We show that TAF/LEN resulted in a complete and durable response of the DLCL by PET/CT and a complete bone marrow response of lymphoplasmacytoid cells, including the normalization of complex cytogenetic abnormalities. The extraordinary response of our patient to TAF/LEN suggests that this combination may be an effective and tolerable therapy for transformed WM as well as relapsed or refractory non-transformed WM. Clinical trials of TAF/LN for the treatment of Waldenström macroglobulinemia are recommended.

Treatments for Relapsed-Refractory Diffuse Large B-cell Lymphoma: A Preliminary Evaluation of the Place in Therapy of Glofitamab, a Bispecific Monoclonal Antibody.

Background and objectives Glofitamab, tafasitamab, loncastuximab tesirine, polatuzumab, and selinexor have been proposed for the treatment of relapsed-refractory diffuse large B-cell lymphoma (DLBCL). We studied the pattern of overall survival (OS) for these five agents. Methods We reconstructed patient-level data from the Kaplan-Meier OS graphs published in five pivotal trials. For this purpose, we used an artificial intelligence technique (the Shiny method). Reconstructed survival curves were subjected to standard statistics to perform cross-trial indirect comparisons; medians and hazard ratios (HRs) with 95% confidence interval (CI) were estimated for each treatment. Results Using glofitamab (a bispecific antibody) as a common comparator, our analysis of OS yielded the following results: a) tafasitamab plus lenalidomide, HR: 0.514 (95% CI: 0.341 to 0.776; P=0.0015); b) polatuzumab vedotin, HR: 0.822 (95% CI: 0.509 to 1.327); c) selinexor, HR: 1.170 (95% CI: 0.852 to 1.603); and d) loncastuximab tesirine, HR: 1.120 (95% CI: 0.868 to 1.659). Medians were estimated as follows: a) tafasitamab plus lenalidomide, 26.5 months (95% CI: 18.9 to NA); b) polatuzumab vedotin, 12.5 months (95% CI: 9.03 to NA); c) glofitamab, 11.7 months (95% CI: 7.96 to 18.0); d) loncastuximab tesirine, 10.2 months (95% CI: 6.97 to 11.6); and e) selinexor, 10.1 months (95% CI: 6.72 to 14.2). Conclusions These comparative results represent an original finding generated by the Shiny method. Although these comparisons are indirect, our analysis offers a useful synthesis of the outcomes of these treatments. According to these results, glofitamab, despite its improved mechanism of action, does not seem to confer any OS advantage compared with the other four treatments.

Economic evaluation of polatuzumab-bendamustine-rituximab vs. tafasitamab-lenalidomide in transplant-ineligible R/R DLBCL.

AIM: Polatuzumab vedotin-bendamustin-rituximab (PBR) and tafasitamab-lenalidomide (Tafa-L) were approved recently for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in autologous stem cell transplant (ASCT) ineligible patients. We performed an industry-independent pharmacoeconomic evaluation of both regimens over a 5-year (y) time horizon (US payer perspective; 2020 USD). METHODS: Survival curves, treatment costs, and utility values were applied in a three-state Markov model (progression-free survival (PFS), post-progression survival (PPS), death) to estimate the incremental follow-up (ICER) and cost-utility ratios (ICUR). A novel metric of the incremental cost per 1% gain in the probability of achieving objective response (OR), PFS, and OS were estimated. RESULTS: Five-year Tafa-L costs ($470,119) exceeded PBR's ($249,217) by $220,902 with incremental gains of 0.71 life-years (LY) and 0.32 quality-adjusted life-years (QALY); yielding ICER of $310,041/LYg and ICUR of $694,241/QALYg. Tafa-L had favorable PFS and OS rates over PBR with adjusted differences of +19.2 and +34.1%, respectively at trial follow-up (∼2 years), with corresponding 5 years differences in survival of +7.8% in PFS and +21.4% in OS. The incremental cost per 1% gain in the probability of achieving OR, PFS and OS at follow-up were $8,479, $6,359, and $3,583; and $28,321 and $10,323 for PFS and OS at 5 years. CONCLUSION: The sustained Tafa-L treatment demonstrated better survival outcomes than 6-cycle PBR though at a greater cost. The incremental costs to gain a 1% improvement in 2 and 5 years survival outcomes with Tafa-L over PBR were modest, underscoring the longer-term benefit of Tafa-L over PBR in patients ineligible for or opting out of ASCT.

PLAIN LANGUAGE SUMMARYTwo new medication regimens were approved recently for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL): six cycles of polatuzumab vedotin-bendamustine-rituximab (PBR) and continuous twice-monthly treatment with tafasitamab-lenalidomide (Tafa-L). Both treatments are expensive, but Tafa-L more so because it requires continuous treatment versus the maximum 6 cycles of PBR. However, Tafa-L may have better progression-free (PFS) and overall survival (OS) outcomes. Is this worth the additional money?We conducted a cost-effectiveness analysis comparing Tafa-L to PBR. After calculating the differenced in costs and the progression-free and overall survival, we determined the additional cost to gain a life year (LY) or quality-adjusted life year (QALY) over 5 years. We also introduced a novel metric: how much it would cost extra to gain, with Tafa-L treatment, an improvement in progression-free or overall survival of 1% over the survival afforded by PBR. Treatment with Tafa-L over PBR would cost an extra $220,902 for a gain of 0.71 life years (standardized, $310,041/LYgained) and 0.32 quality-adjusted life years ($694,241/QALYgained). Importantly, two years of Tafa-L treatment increased the likelihood of progression-free survival by +19.2% and overall survival by 34.1% over PBR; extending to +7.8% in progression-free survival and +21.4% in overall survival at five years. It cost an additional $28,321 per 1% gain in likelihood in progression-free survival and $10,323 per 1% gain in overall survival after 5 years. Summarized, the increased costs of Tafa-L translate into significantly better progression-free and overall survival.

Tafasitamab for refractory/relapsed diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common lymphoproliferative and invasive disease. The current first-line regimen for the treatment of DLBCL is R-CHOP, which is the combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. R-CHOP has significantly improved the outcome of DLBCL in the last decades. However, 30-40% of patients fail the therapy with R-CHOP. Salvage chemotherapy for relapsed/refractory DLBCL (R/R DLBCL) is extremely challenging, especially in elderly patients. In July 2020, a new monoclonal antibody, tafasitamab, was approved by the Food and Drug Administration (FDA) of the United States for the treatment of DLBCL. Tafasitamab is an anti-CD19 monoclonal antibody which is Fc-enhanced and humanized. CD19 is typically expressed in the developing B cells in non-Hodgkin's lymphomas. Tafasitamab has been proven to be a safe and valid treatment and recommended to be used in combination with lenalidomide in adults with R/R DLBCL who are ineligible for autologous stem cell transplantation (ASCT). This article evaluates the pharmacodynamics, pharmacokinetics, mechanism of action and the clinical application of tafasitamab in the treatment of DLBCL, particularly in R/R DLBCL. The advantages and disadvantages of using tafasitamab and chimeric antigen receptor T cells (CAR-T cells) targeting CD19 are also discussed.