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European Hematology Association (EHA) Annual Congress | 2024 | News | Updates | iPharmaCenter

Updated: Jun 18

Vertex Presented Long-Term Data on Casgevy (Exagamglogene Autotemcel) at 2024 EHA Congress

Vertex Pharmaceuticals has unveiled extended data on Casgevy (exagamglogene autotemcel) from international clinical trials involving patients with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT).

Casgevy stands as the first and sole CRISPR-based gene-editing therapy approved for these conditions.


The presentation included data from over 100 patients (46 with SCD and 56 with TDT) treated with exa-cel, with the longest follow-up period surpassing five years. The efficacy results align with previously reported primary and secondary endpoints, showcasing sustained clinical benefits and stable levels of fetal hemoglobin (HbF) and allelic editing.


Key Data from CASGEVY Pivotal Trials:

In SCD:

  • 36 out of 39 evaluable patients (92.3%) with at least 16 months of follow-up remained free from vaso-occlusive crises (VOCs) for a minimum of 12 consecutive months (VF12), consistent with prior primary endpoint data. The average duration without VOCs was 27.9 months, with a maximum of 54.8 months.

  • 38 out of 39 patients (97.4%) with at least 16 months of follow-up were free from hospitalizations related to VOCs for at least 12 consecutive months (HF12), matching previously reported secondary endpoint data.


In TDT:

  • 49 out of 52 evaluable patients (94.2%) with at least 16 months of follow-up achieved transfusion independence for at least 12 consecutive months, with a mean weighted hemoglobin of at least 9 g/dL (TI12), consistent with earlier primary endpoint data. The average duration of transfusion independence was 31.0 months, with a maximum of 59.4 months.

  • All TDT patients with at least 16 months of follow-up were free from transfusions.

  • Two of the three patients who did not achieve TI12 in the CLIMB-111 study reached TI12 in the long-term follow-up study, CLIMB-131, maintaining transfusion independence for over a year. The third patient has been transfusion-free for 3.4 months.

Both SCD and TDT patients experienced sustained, clinically significant improvements in quality of life, encompassing physical, emotional, social/family, and functional well-being, as well as overall health.


Additional Findings:

  • In both SCD and TDT patients, stable edited levels of BCL11A alleles were observed over time in bone marrow and peripheral blood, indicating successful long-term editing in hematopoietic stem cells.

  • All patients showed successful neutrophil and platelet engraftment post-exa-cel infusion.

  • The safety profile of exa-cel was generally in line with expectations for myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.


The data confirm the promising potential of CASGEVY in providing durable clinical benefits for patients with severe SCD and TDT.

 

Updated linvoseltamab data show continued improvement in responses for heavily pre-treated multiple myeloma patients

Regeneron has unveiled new 14-month median follow-up data from the pivotal Phase 1/2 LINKER-MM1 trial of linvoseltamab, targeting patients with relapsed/refractory (R/R) multiple myeloma (MM).


The updated data for linvoseltamab at a 200 mg dose among 117 patients underscores the durability and depth of responses observed in previous analyses.

Key results from the presentation and publication include:


  • A 71% objective response rate (ORR), with 50% of patients achieving a complete response (CR) or better and 63% achieving a very good partial response (VGPR) or better, as assessed by an independent review committee.

  • A median duration of response (DoR) of 29 months for all responders, while the median DoR was not reached for those achieving a CR or better. Non-pre-specified analyses indicated an 81% and 95% probability of maintaining a response at 12 months for all responders and those with a CR or better, respectively.

  • Median progression-free survival (PFS) was not reached, with a 70% probability of being progression-free at 12 months among all patients. For those with a CR or better, the estimated probability was 96%.

  • Median overall survival (OS) was 31 months for all patients. In non-pre-specified analyses, the median OS was not reached for patients with a CR or better, with a 75% and 100% probability of survival at 12 months for all patients and those with a CR or better, respectively.

  • High CR rates in specific subgroups: 55% in patients aged 75 or older, 48% in those with high cytogenetic risk, 45% in Black or African American patients, and 28% in patients with plasmacytomas.


Safety data at the 14-month median follow-up were consistent with those at the 11-month mark. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event (TEAE), occurring in 46% of patients, with 35% experiencing Grade 1, 10% experiencing Grade 2, and one case (1%) experiencing Grade 3 CRS.


 

Elrexfio Achieves Over Two-Year Median Overall Survival in Relapsed or Refractory Multiple Myeloma


Pfizer has shared detailed overall survival (OS) findings from its Phase 2 MagnetisMM-3 study, revealing that Elrexfio (elranatamab) demonstrated a median OS of 24.6 months in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM). These results come from cohort A (n=123) of the pivotal single-arm trial.


After more than two years of follow-up in the MagnetisMM-3 trial, the overall response rate (ORR) for patients on ELREXFIO was 61.0%, with a complete response rate (CRR) of 37.4%.

Responses have continued to deepen over time, and the median duration of response (DOR) has not yet been reached. At the two-year mark, the estimated DOR rate was 66.9% for all responders and 87.9% for patients achieving a complete response or better.

Median progression-free survival (PFS) was 17.2 months, while for those with a complete response or better, the median PFS was not reached. At two years, the estimated PFS rate was 90.6%.



The safety and tolerability profile of Elrexfio in the MagnetisMM-3 trial remained consistent with previous observations. Five patients (4.1%) developed secondary primary malignancies (SPMs), all of which were squamous cell carcinoma of the skin, a common occurrence in multiple myeloma patients. No hematological SPMs were reported. Due to the risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after the administration of each of the two step-up doses in the Elrexfio dosing schedule, and they should remain near a healthcare facility during this period.


Elrexfio received accelerated approval from the U.S. Food and Drug Administration in August 2023 for treating adult patients with RRMM who have undergone at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. This approval was based on the positive results from the MagnetisMM-3 trial.

 

Calquence with Chemoimmunotherapy Shows Significant Improvement in Survival for Untreated Mantle Cell Lymphoma in ECHO Phase III Trial

AstraZeneca’s Calquence Combines with Chemoimmunotherapy to Reduce Risk of Disease Progression or Death by 27%


AstraZeneca has announced promising results from the Phase III ECHO trial, demonstrating that Calquence (acalabrutinib) combined with bendamustine and rituximab significantly improves progression-free survival (PFS) and shows a favorable trend in overall survival (OS) for patients with previously untreated mantle cell lymphoma (MCL) compared to the standard chemoimmunotherapy regimen.



The trial results revealed that the combination of Calquence, bendamustine, and rituximab reduced the risk of disease progression or death by 27% compared to the standard chemoimmunotherapy.

Patients receiving the Calquence combination had a median PFS of 66.4 months, compared to 49.6 months for those on standard chemoimmunotherapy.


The secondary endpoint of overall survival (OS) also showed a positive trend for the Calquence combination, supporting its clinical benefits. However, the OS data were not fully mature at the time of analysis, and further assessment will continue as the trial progresses.



Enrollment for the ECHO trial occurred during the COVID-19 pandemic, necessitating a pre-specified analysis that accounted for COVID-19-related deaths. This analysis indicated an even greater improvement in PFS for both treatment groups, with the Calquence combination reducing the risk of disease progression or death by 36%.

In this analysis, the median PFS for patients on the Calquence combination was not reached, compared to 61.6 months for the standard chemoimmunotherapy group.

Additionally, a favorable OS trend was observed for the Calquence combination in this context.


The safety profile of Calquence was consistent with previously known data, with no new safety concerns identified. Grade 3 or higher adverse events (AEs) occurred in 88.9% of patients treated with the Calquence combination and 88.2% of those on standard chemoimmunotherapy.


 

Roche’s Phase III STARGLO Study Shows Columvi Significantly Improves Survival in Relapsed or Refractory Diffuse Large B-Cell Lymphoma


Roche has announced that its Phase III STARGLO study has yielded statistically significant and clinically meaningful results for Columvi (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) compared to rituximab combined with GemOx (R-GemOx) for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This study focused on patients who have received at least one prior line of therapy and are ineligible for autologous stem cell transplant or have undergone two or more prior therapies.


The primary analysis, with a median follow-up of 11.3 months, demonstrated that the study met its primary endpoint of overall survival (OS). Patients treated with the Columvi and GemOx combination showed a 41% reduction in the risk of death compared to those receiving R-GemOx. The median OS was not reached for the Columvi regimen, while it was nine months for the R-GemOx group. The safety profile of the Columvi combination was consistent with the known profiles of the individual drugs.



Exploratory subgroup analyses showed consistent results across various clinically relevant factors, such as the line of therapy (second-line versus third-line+) and the outcome of the last therapy (relapsed versus refractory). Although some regional inconsistencies were noted, these were considered limited due to the exploratory nature of the analysis and small subgroup sizes.


The Columvi combination also achieved its key secondary endpoints, including a 63% reduction in the risk of disease progression or death (progression-free survival, PFS) compared to R-GemOx. In a follow-up analysis with a median follow-up of 20.7 months, continued benefits were observed in both primary and secondary endpoints. The median OS for patients treated with the Columvi combination was 25.5 months, nearly double the 12.9 months seen with R-GemOx. Additionally, more patients experienced a complete response with the Columvi combination (58.5%) compared to R-GemOx (25.3%).


Adverse event (AE) rates were higher with the Columvi combination, which may be attributed to the higher median number of treatment cycles received (11 versus 4 for R-GemOx). One common AE was cytokine release syndrome, which was mostly low grade and occurred primarily during the first treatment cycle.


Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial, highlighting the potential of this therapeutic combination to improve survival outcomes in earlier lines of treatment. Historically, second-line therapy for R/R DLBCL involved high-dose chemotherapy followed by stem-cell transplant, but many patients are ineligible due to age or medical conditions. While newer therapies are emerging, there remain barriers to access, and alternative treatment options are crucial. Columvi, administered as a fixed-duration treatment, offers patients a defined treatment period and the potential for a treatment-free interval, unlike continuous therapies.


The STARGLO study is a Phase III, multicenter, open-label, randomized trial evaluating the efficacy and safety of Columvi in combination with GemOx versus rituximab with GemOx in patients with relapsed or refractory DLBCL who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. The study's outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.


The STARGLO study is intended to confirm and potentially convert Columvi's accelerated approval in the US and conditional marketing authorization in the EU to full approvals for patients with R/R DLBCL after two or more lines of systemic therapy, building on the pivotal Phase I/II NP30179 study.

 

Kite Unveils New Findings on Yescarta at EHA 2024, Highlighting Early Treatment Benefits

Key Insights from Clinical and Real-World Data on Yescarta for Relapsed/Refractory Large B-cell Lymphoma

  • Early Treatment Advantages: New analysis indicates Yescarta manufacturing in second-line therapy reduces leukapheresis-to-infusion time compared to third-line+ treatment.

  • Positive Patient Outcomes: Data supports improved patient outcomes with timely infusion.

  • Outpatient Safety: Preliminary results show outpatient administration of Yescarta and Tecartus is safe and feasible.


Santa Monica, Calif. – Kite, a subsidiary of Gilead, has released new findings on Yescarta (axicabtagene ciloleucel) at the 2024 European Hematology Association (EHA) Annual Congress in Madrid. The analyses encompass clinical research and real-world evidence, emphasizing Yescarta’s manufacturing efficiency and the potential benefits of early treatment for relapsed/refractory large B-cell lymphoma (LBCL). A


Clinical and Real-World Insights

The research includes a comparative study (abstract P1425) demonstrating higher manufacturing success rates and enhanced T-cell performance for Yescarta when used as a second-line treatment, compared to third-line or beyond. Efficient CAR T-cell therapy manufacturing is crucial as it shortens the time from leukapheresis to cell infusion.


Manufacturing Experience

An analysis involving 4,175 patients compared real-world and clinical trial data for second-line and third-line+ treatments. It revealed a significant improvement in first-pass manufacturing success rates (FP-MSR) for second-line treatment (95.08%) versus third-line+ (92.48%). This indicates 26 more successful manufacturing attempts per 1,000 for second-line treatments, crucial for reducing multiple manufacturing attempts and potentially shortening the time to infusion.


The study also compared the median percentage of naïve-like T-cells in leukapheresis between ZUMA-1 (third-line) and ZUMA-7 (second-line) trials. Second-line patients exhibited nearly twice as many naïve-like T-cells, suggesting earlier intervention captures a higher proportion of these cells, associated with better response rates.


Outpatient Administration Studies

Kite is also presenting studies on the outpatient administration of Yescarta and Tecartus, evaluating safety and effectiveness.

ZUMA-24 Study

The ZUMA-24 Phase 2 study investigates Yescarta’s outpatient administration with prophylactic corticosteroids in R/R LBCL patients. Preliminary results from 30 patients over a five-month median follow-up indicate the safety and efficacy are consistent with prior studies.


Outpatient Trends

A real-world study at Mayo Clinic assessed outpatient administration of Yescarta and Tecartus, focusing on safety endpoints like CRS and ICANS, along with hospitalization rates. The findings affirm that outpatient administration is viable without increased toxicity.


About Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy approved for treating:

  • Adult patients with LBCL refractory to first-line chemoimmunotherapy or relapsed within 12 months.

  • Adult patients with R/R LBCL after two or more systemic therapies, including various types of LBCL.

  • Adult patients with R/R follicular lymphoma (FL) after two or more systemic therapies, under accelerated approval based on response rate, with continued approval dependent on further clinical benefits.


These comprehensive analyses presented at the EHA 2024 underscore the potential benefits of administering Yescarta earlier in the treatment process for LBCL, highlighting improved manufacturing success rates and patient outcomes, along with the feasibility of outpatient care.

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