Genentech's Fixed-Duration Therapy Columvi and Lunsumio Showed Promise in Lymphoma Patients
New data presented at the American Society of Hematology (ASH) 2024 conference highlight the potential of Genentech's fixed-duration treatments, Columvi and Lunsumio, to improve outcomes for patients with lymphoma. Long-term follow-up studies confirm sustained remission rates and reduced treatment burden, while innovative delivery methods are being explored to enhance patient experience.
Key Findings:
Durable Remission: Both Columvi and Lunsumio demonstrated long-lasting remission rates, with a significant proportion of patients remaining disease-free beyond the treatment period.
Reduced Treatment Burden: Real-world data suggest that the fixed-duration treatment approach can lead to fewer treatment cycles and decreased patient burden.
Innovative Delivery: The initial presentation of subcutaneous Lunsumio showcased non-inferiority to intravenous administration, potentially offering a more convenient outpatient option.
A three-year follow-up of the pivotal Phase II NP30179 study evaluating Columvi in patients with relapsed or refractory large B-cell lymphoma (LBCL) revealed encouraging results.
Forty percent of participants achieved a complete response (CR), with a median duration of CR exceeding 29 months. Notably, a significant portion of patients who were in complete remission at the end of treatment remained disease-free two years post-therapy. The safety profile remained consistent with previous findings.
Long-term data from the pivotal Phase II GO29781 study of Lunsumio in patients with relapsed or refractory follicular lymphoma (FL) demonstrated sustained remission rates. Nearly two-thirds of patients with a CR were alive and disease-free at 45 months.
The overall response rate and complete response rates in the overall population were 77.8% and 60.0%, respectively.
These positive results were observed even in patients with a history of rapid disease progression, a typically challenging patient group. No new safety concerns emerged.
Blenrep Shows Notable Survival Advantage, Cutting Death Risk by 42% in Relapsed Multiple Myeloma
Blenrep, when used in combination with bortezomib and dexamethasone (BVd), has demonstrated a significant improvement in overall survival for patients with multiple myeloma who have experienced a relapse or are resistant to prior treatment.
Results from the DREAMM-7 clinical trial revealed a 42% reduction in the risk of death compared to treatment with daratumumab, bortezomib, and dexamethasone (DVd).
The survival benefit appeared early and was sustained throughout the follow-up period.
These findings reinforce earlier data from the DREAMM-7 and DREAMM-8 trials, which highlighted substantial improvements in progression-free survival (PFS) when using Blenrep-based combinations compared to standard treatment options. The promising results suggest Blenrep combinations could become a new standard of care. Currently, these combinations are under regulatory review in seven major markets.
DREAMM-7 Trial Results
The DREAMM-7 trial is a Phase III study assessing Blenrep (belantamab mafodotin) with bortezomib and dexamethasone against daratumumab with the same combination (DVd) as a second-line or later treatment for relapsed or refractory multiple myeloma. With a median follow-up of 39.4 months, the analysis indicated a 42% lower risk of death for patients receiving the Blenrep combination (243 patients) compared to the daratumumab group (251 patients).
Although median overall survival (mOS) was not reached in either group, the projected mOS for the BVd group was 84 months, compared to 51 months for the DVd group. After three years, 74% of patients treated with BVd were alive, compared to 60% of those treated with DVd. The survival advantage became apparent as early as four months and continued throughout the study, reflected in the separation of survival curves.
In addition to improved overall survival, the Blenrep combination achieved a higher rate of minimal residual disease (MRD) negativity, indicating the absence of detectable cancer cells. This MRD negativity rate was more than 2.5 times higher than that of the daratumumab combination and was confirmed as statistically significant following the survival results (p<0.00001). These outcomes suggest the potential for more effective and lasting disease control with Blenrep-based therapy.
The Blenrep combination also delivered clinically meaningful improvements in other key endpoints, including duration of response (DOR) and progression-free survival 2 (PFS 2). These findings point to deeper and more durable responses compared to the daratumumab-based treatment.
Belantamab mafodotin + bortezomib + dexamethasone (BVd) | Daratumumab + bortezomib + dexamethasone (DVd) | |
OS rate at 24 months | 79% | 67% |
OS rate at 36 months | 74% | 60% |
Minimal residual disease | 25.1% | 10.4% |
Overall response rate | 83.1% | 71.3% |
Complete response | 35.8% | 17.5% |
Median DOR (duration of response) | 40.8 months | 17.8 months |
About the DREAMM-7 Study
DREAMM-7 is a multicenter, open-label, randomized Phase III trial designed to evaluate the safety and effectiveness of Blenrep combined with bortezomib and dexamethasone (BVd) versus daratumumab combined with bortezomib and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma. Participants had received at least one prior therapy and showed disease progression during or after their last treatment.
The study enrolled 494 patients, randomized equally between the two treatment arms. Blenrep was administered intravenously at a dose of 2.5 mg/kg every three weeks. The primary endpoint was progression-free survival, assessed by an independent review committee. Secondary endpoints included overall survival, duration of response, MRD negativity, overall response rate, safety, and quality of life metrics.
Merck’s Zilovertamab Vedotin Combined With R-CHP Achieves 100% Complete Response in Phase 2 Trial for Untreated Diffuse Large B-Cell Lymphoma
Merck has shared the first findings from the Phase 2 waveLINE-007 study, which investigates zilovertamab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as a treatment for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
The results showed that zilovertamab vedotin at a 1.75 mg/kg dose achieved a 100% complete response (CR) rate.
About the waveLINE-007 Trial
WaveLINE-007 is an open-label, non-randomized Phase 2 study evaluating the safety and efficacy of zilovertamab vedotin, an experimental antibody-drug conjugate targeting ROR1, in combination with R-CHP for untreated DLBCL patients.
The primary objectives include assessing safety, dose-limiting toxicities, adverse events, and CR rates according to the Lugano Response Criteria. Secondary goals include evaluating overall response rate (ORR) and duration of response (DOR).
A total of 36 participants were enrolled, receiving intravenous infusions of zilovertamab vedotin with R-CHP on day one of each 21-day cycle, for up to eight cycles. The study included three dose levels of zilovertamab vedotin:
1.75 mg/kg group (15 patients): All completed the treatment.
2.0 mg/kg group (15 patients): 14 completed treatment; one discontinued after the first cycle due to physician decision.
2.25 mg/kg group (6 patients): 5 completed treatment; one discontinued due to physician decision.
Efficacy Results
1.75 mg/kg group: 100% CR rate
2.0 mg/kg group: 93.3% CR rate
2.25 mg/kg group: 100% CR rate
Overall, the CR rate for all patients at the end of treatment was 97.2%. The median follow-up period was 17.6 months (ranging from 7.1 to 24.6 months). The ORR mirrored the CR rates, achieving 100% in the 1.75 mg/kg and 2.25 mg/kg groups and 93.3% in the 2.0 mg/kg group. The median DOR was not reached, and the 12-month DOR for all patients was 93.5%.
These promising results confirm 1.75 mg/kg as the recommended dose for Phase 3 trials, highlighting the potential of zilovertamab vedotin combined with R-CHP as an effective treatment option for previously untreated DLBCL patients.
Extended Data for Scemblix Demonstrates Superior Efficacy and Favorable Safety in Newly Diagnosed CML
Longer-term findings for Scemblix (asciminib) indicate continued superior efficacy and a favorable safety profile in adults with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP).
Data from the Phase III ASC4FIRST trial show that Scemblix achieved higher major molecular response (MMR) rates compared to both investigator-selected tyrosine kinase inhibitors (TKIs) and imatinib alone at the 96-week evaluation.
Scemblix achieved a significantly higher MMR rate of 74.1% compared to 52% for investigator-selected TKIs, meeting key secondary endpoints of the trial. When compared specifically to imatinib, the MMR rate for Scemblix was 76.2% versus 47.1%, highlighting its superior performance.
Furthermore, Scemblix showed a notable 15.1% higher MMR rate compared to second-generation (2G) TKIs like nilotinib, dasatinib, and bosutinib (72% versus 56.9%). These results reinforce Scemblix’s effectiveness as a frontline treatment option for newly diagnosed patients.
About the ASC4FIRST Trial
ASC4FIRST is a pivotal Phase III study comparing the efficacy and safety of Scemblix with a range of investigator-selected TKIs, including imatinib, nilotinib, dasatinib, and bosutinib.
The trial focused on adults newly diagnosed with Philadelphia chromosome-positive CML-CP.
The primary analysis took place at 96 weeks, with a median follow-up period of 2.2 years. Results showed that more patients treated with Scemblix achieved deeper molecular responses (MR4 and MR4.5) compared to those receiving other TKIs.
These long-term results underscore Scemblix’s potential to improve outcomes while maintaining a manageable safety profile for patients with newly diagnosed CML.
Lilly's pirtobrutinib showed significant reduction in disease progression or death in CLL or SLL patients
A Phase 3 clinical trial, BRUIN CLL-321, has shown that pirtobrutinib significantly reduces the risk of disease progression or death in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously received covalent BTK inhibitor therapy.
Compared to treatments using idelalisib plus rituximab or bendamustine plus rituximab, pirtobrutinib lowered the risk by 46%.
Improved Time to Next Treatment
Patients treated with pirtobrutinib achieved a median time of 23.9 months before needing additional treatment or experiencing death, compared to 10.9 months for those in the control group. This study marks the first randomized Phase 3 trial in CLL specifically targeting patients who had prior exposure to BTK inhibitors.
Study Design and Patient Profile
The BRUIN CLL-321 trial included 238 participants who were randomized into two groups: one receiving pirtobrutinib (119 patients) and the other receiving either idelalisib plus rituximab or bendamustine plus rituximab (119 patients). The patients in both groups had undergone a median of three prior treatments, all involving at least one covalent BTK inhibitor. Additionally, about half had previously been treated with venetoclax. Many patients presented with aggressive disease markers, such as TP53 mutations, 17p deletions, unmutated IGHV status, or complex karyotypes.
Efficacy Results
The analysis, based on independent review committee (IRC) assessment and data up to August 29, 2024, showed a median progression-free survival (PFS) of 14.0 months for the pirtobrutinib group compared to 8.7 months in the control group.
The hazard ratio (HR) for disease progression or death was 0.54, indicating a 46% reduction in risk. This benefit was consistent across patients with high-risk characteristics, including prior venetoclax treatment, TP53 mutations, 17p deletions, and other poor prognosis factors.
Secondary Outcomes
Pirtobrutinib also showed improvements in several secondary outcomes:
Investigator-Assessed PFS: Median of 15.3 months with pirtobrutinib vs. 9.2 months in the control group (HR: 0.48).
Event-Free Survival (EFS): Median of 14.1 months with pirtobrutinib vs. 7.6 months in the control group (HR: 0.39).
Time to Next Treatment (TTNT) or Death: Median of 23.9 months with pirtobrutinib vs. 10.9 months in the control group (HR: 0.37).
Among those eligible for crossover, 76% of patients in the control group (50 out of 66) switched to pirtobrutinib after disease progression.
BRUIN CLL-321 is an open-label, randomized Phase 3 trial comparing pirtobrutinib to standard treatments of idelalisib plus rituximab or bendamustine plus rituximab in patients with CLL or SLL who had prior BTK inhibitor therapy. Patients received either 200 mg of pirtobrutinib orally once daily or one of the control treatments at prescribed doses. The primary objective was to measure PFS based on the 2018 International Workshop on CLL criteria. Secondary goals included overall response rate (ORR), duration of response (DoR), event-free survival, overall survival (OS), time to next treatment, safety, and patient-reported outcomes.
These results highlight pirtobrutinib as a promising option for patients with relapsed or refractory CLL/SLL who have limited treatment alternatives.
Real-World Early Results for Second-Line Yescarta Therapy in Patients With Relapsed or Refractory Large B-Cell Lymphoma
A comprehensive real-world study involving 446 patients across 89 U.S. centers analyzed outcomes for individuals with relapsed or refractory large B-cell lymphoma (LBCL). This population included those with diffuse large B-cell lymphoma (DLBCL) (78%), primary mediastinal B-cell lymphoma (PMBCL) (3%), high-grade B-cell lymphoma (18%), and grade IIIB follicular lymphoma (1%). These patients received second-line axicabtagene ciloleucel (Axi-Cel) treatment, and the results were comparable to the findings of the ZUMA-7 trial, despite a broader range of patient profiles and disease characteristics. The median follow-up duration was 12 months.
Overall Response and Survival Rates
The overall response rate (ORR) for all patients was 79%, with a complete response (CR) rate of 64%. At 12 months, the duration of response (DOR) was 66%, progression-free survival (PFS) was 53%, event-free survival (EFS) was 53%, and overall survival (OS) reached 71%. Side effects included cytokine release syndrome (CRS) in 87% of patients (5% experiencing grade 3 or higher) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 50% (22% experiencing grade 3 or higher).
Outcomes Based on ZUMA-7 Eligibility
Patients were grouped based on eligibility criteria for the ZUMA-7 trial. For those deemed ineligible for ZUMA-7 (219 patients), the ORR was 79%, with a CR rate of 63%. In patients who met ZUMA-7 eligibility criteria or whose eligibility was unknown (214 patients), the ORR was also 79%, with a CR rate of 65%. At the 12-month mark:
Duration of Response (DOR): 60% in ineligible patients vs. 69% in eligible/unknown patients.
Progression-Free Survival (PFS): 48% in ineligible patients vs. 58% in eligible/unknown patients.
Event-Free Survival (EFS): 48% in ineligible patients vs. 58% in eligible/unknown patients.
Overall Survival (OS): 62% in ineligible patients vs. 80% in eligible/unknown patients.
The occurrence of ICANS was higher in ineligible patients (54%) compared to eligible or unknown patients (45%).
Results for Primary Mediastinal B-Cell Lymphoma (PMBCL)
In a subgroup of 13 patients with PMBCL, the ORR was 69%, with all achieving a complete response. At six months:
Duration of Response (DOR): 100%
Progression-Free Survival (PFS): 68%
Event-Free Survival (EFS): 68%
Overall Survival (OS): 100%
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