Gina Mauro

Real-world data from the U.S. confirms the effectiveness of Monjuvi for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The real-world effectiveness of Monjuvi (tafasitamab-cxix) in U.S. patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was confirmed, along with factors associated with survival, according to data from a retrospective medical chart review presented at the 

At a median follow-up time of 14.7 months from Monjuvi initiation, the real-world progression-free survival (PFS) with Monjuvi was 11.3 months in the overall population (181 patients), and the real-world overall survival (OS) was 24.8 months. The real-world overall response rate (ORR) to the agent was 73.5%, which comprised a complete response (CR) rate of 23.2% and a partial response (PR) rate of 50.3%. In the patients who achieved a real-world CR or PR with the agent (133 patients), the real-world duration of response (DOR) was 9.6 months.

An analysis showed that factors significantly linked with increased risk of progression included receiving the agent in the third to fifth line (51 patients) versus the second line (130 patients), having Ann Arbor stage 3 to 4 disease (169 patients) versus stage 1 to 2 (10 patients), increasing Charlson Comorbidity Index scores (181 patients) and bulky (36 patients) versus non-bulky (145 patients) disease.

Moreover, factors significantly associated with increased risk of mortality included receiving Monjuvi in the third to fifth line versus the second line, increasing age, ECOG performance status of 2 or higher versus below 2 and bulky versus non-bulky disease.

Progression-free survival (PFS): time without disease worsening.

Overall survival (OS): time until death from any cause.

Overall response rate (ORR): percentage of patients with tumor reduction.

Complete response (CR): no detectable cancer.

Partial response (PR): tumor reduction, but not complete.

Duration of response (DOR): time response lasts.

Stable disease (SD): cancer neither grows nor shrinks.

Ann Arbor stage: system to classify lymphoma spread.

Charlson Comorbidity Index scores: predicts mortality based on comorbidities.

Non-bulky disease: small or no large tumor mass.

ECOG performance status: measures a patient's ability to perform daily activities, with scores from 0 (fully active) to 5 (dead). Higher scores indicate greater impairment.

“The additional follow-up from the initial data collection allowed for a more robust evaluation of the real-world effectiveness of [Monjuvi] in patients with relapsed or refractory DLBCL, predominantly in the community practice setting,” lead study author Dr. Kim Saverno of Incyte Corporation, in Wilmington, Delaware, said in a poster presentation of the data. “These results support a real-world clinical benefit for [Monjuvi], with the greatest benefit observed when [the agent] was received in second versus later lines of therapy.”

Additional treatment outcome data showed that in those who received Monjuvi in the second line (130 patients), the real-world ORR was 78.5%; this was comprised of a CR rate of 27.7% and a PR rate of 50.8%. For this group, the stable disease (SD) rate was 8.5%, the progressive disease (PD) rate was also 8.5%, and 4.6% of patients did not have these data available. In the group of patients who received the immunotherapy in the third line (43 patients), the real-world ORR was 62.8%; this comprised a CR rate of 11.6% and a PR rate of 51.2%. In this subset, the SD and PD rates were 18.6% and 11.6%, respectively; 7% of patients did not have these data available.

In patients who experienced a real-world CR as a best response to Monjuvi (42 patients), the median real-world DOR was 19.2 months. In those who achieved a real-world PR as a best response to the agent (91 patients), the median real-world DOR was 8.5 months.

The CD19-targeted immunotherapy Monjuvi was approved by the FDA in July 2020 for use in combination with Revlimid (lenalidomide) in adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma and who are not candidates to undergo autologous stem cell transplant. To date, few studies have evaluated the agent in a US real-world setting, according to Saverno. She added that data from a real-world study were previously shared, but had a limited follow-up time of 6.5 months, which “precluded robust evaluations of the clinical effectiveness” of the agent.

For patients to be considered eligible for the analysis, they must have started treatment with Monjuvi with or without concomitant Revlimid for relapsed or refractory disease on or following Oct. 21, 2020; be at least 18 years old at the time treatment with the agent was started; and have undergone at least four months of follow-up since treatment started. Those who died during this four-month interval were still permitted. If patients received the agent as part of an interventional clinical trial, they were excluded.

A total of 181 patients were included in the study; 144 of these patients were still alive at last follow-up of initial data collection which had occurred between Feb. 22, 2023, and March 29, 2023. Of those patients, 137 patients had additional follow-up data available and underwent additional data collection between Dec. 18, 2023, and Jan. 31, 2024. A total of 106 patients were alive at last follow-up.

“Over 70% of patients received [Monjuvi] in the second line, and 71% of patients had discontinued [Monjuvi] at the last follow-up, mostly due to disease progression,” Saverno noted. “Over half of the patients were still alive at the last follow-up, and among the patients still alive, half [were] still receiving [Monjuvi] at the time of the most recent follow-up.”

In the 181 total patients, the median age at the time of Monjuvi initiation was 71.1 years. Most patients were White (64.1%), and more than half of patients were male (56.4%). Regarding Ann Arbor stage at time of treatment initiation, 5.5% had stage 1 or 2 disease, 93.4% had stage 3 or 4 disease; this information was unknown for 1.1% of patients. ECOG performance status at the time of treatment initiation was 0 to 1 for 52.5% of patients and 2 or higher for 47.5% of patients. Revised International Prognostic Index for Diffuse Large B-cell Lymphoma was 3 to 5 for 80.5% of patients and 1 to 2 for 19.5% of patients.

“This study is impacted by limitations inherent to real-world studies, such as unobserved and missing data,” Saverno concluded. “The number of participating oncologists was small and thus may not reflect the treatment patterns of all US oncologists managing patients with DLBCL.”

“Real-world effectiveness of tafasitamab (tafa) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in the United States.” By Dr. Kim Saverno et al, 

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Articles

Monjuvi (tafasitamab-cxix) demonstrates real-world effectiveness in U.S. patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with a progression-free survival of 11.3 months and overall survival of 24.8 months. The study highlights the importance of early-line treatment, as second-line therapy shows better outcomes compared to later lines. Factors such as disease stage, comorbidity index, and performance status significantly impact progression and mortality risks. Despite limitations, the study supports Monjuvi's clinical benefit, especially when administered in earlier treatment lines.

The real-world effectiveness of Monjuvi for relapsed or refractory diffuse large B-cell lymphoma in the U.S. was demonstrated, according to data from a retrospective analysis.

Real-World Data May Confirm Monjuvi’s Efficacy in Large B-Cell Lymphoma

Epkinly monotherapy demonstrated deep responses and a favorable safety profile in patients with heavily pretreated chronic lymphocytic leukemia.

Heavily pretreated patients with chronic lymphocytic leukemia (CLL) showed deep responses when treated with Epkinly (epcoritamab-bysp) monotherapy, according to findings from the EPCORE CLL-1 trial, presented in a press briefing during the 

Results showed that in the expansion cohort, which had a median follow-up of 22.8 months, the overall response rate (ORR) in 21 response-evaluable patients was 67%, and the complete response (CR) rate was 43%. In 15 patients with TP53 aberrations, these rates were 67% and 33%, respectively; in the IGHV-unmutated group of 16 patients, these were 63% and 44%. In 19 patients who were double-exposed to both a BTK and BCL-2 inhibitor, the ORR was 53% and the CR rate was 37%.

In the cycle 1 optimization (C1 OPT) cohort, which had a median follow-up of 2.9 months among 10 evaluable patients, the ORR was 60%, and the CR rate was 10%.

“There was a comparable ORR between the expansion and C1 OPT cohorts, with limited follow-up for C1 OPT efficacy,” explained lead study author Dr. Alexey Danilov, in a press briefing during the meeting. “Simple C1 OPT measures of an additional [step-up dosing], dexamethasone, and adequate hydration decreased the risk and severity of [side effects] of special interest.”

Danilov serves as the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, co-director of the Toni Stephenson Lymphoma Center, and professor in the Division of Lymphoma of the Department of Hematology & Hematopoietic Cell Transplantation, all within City of Hope in Duarte, California.

Overall response rate (ORR): the percentage of patients who have a complete or partial response to treatment, meaning their tumors either disappeared or shrunk after treatment.

Complete response (CR): patients who fully responded to treatment, meaning they no longer have signs or symptoms of cancer.

Cytokine release syndrome (CRS): a condition that occurs when the body overreacts to immunotherapy, which can become life-threatening if not treated immediately.

ECOG performance status: a measurement of how independently patients can perform daily tasks. A status of zero means they can complete tasks independently and a status of 4 means they cannot perform tasks independently.

Immune effector cell-associated neurotoxicity syndrome (ICANS): a side effect of immunotherapies; the body’s reaction that can cause inflammation in the brain.

Clinical tumor lysis syndrome (CTLS): a condition that can be life-threatening, in which cancer cells rapidly break down and release their contents into the bloodstream, leading to complications.

Minimal residual disease (MRD): microscopic traces of cancer cells that remain in the body after treatment.

Partial response (PR): patients whose tumors shrunk but did not completely disappear after treatment.

Stable disease (SD): patients whose cancer did not worsen or improve after treatment.

Progressive disease (PD): patients whose cancer worsened or spread after treatment.

Progression-free survival (PFS): time after treatment when patients live without their disease worsening or spreading.

Overall survival (OS): time patients live, regardless of their disease status, until death of any cause.

Epkinly is a bispecific CD20-directed CD3 T-cell engager, which was 

 for the treatment of adult patients with relapsed or refractory follicular lymphoma following at least two prior lines of systemic therapy.

In the expansion cohort of the Epcore CLL-1 trial, 23 patients were given a step-up dose schedule of 0.16 milligrams (mg) of Epkinly on cycle 1, day 1; 0.8 mg on cycle 1, day 8; and then the first full dose of 48 mg on cycle 1, day 15. Prophylaxis for cytokine release syndrome (CRS) with prednisone was also permitted. The data cutoff date was May 28, 2024, and the median follow-up was 22.8 months.

In the C1 OPT cohort of 17 patients, CRS prophylaxis with dexamethasone and adequate hydration was given. This also included a step-up dose design of 0.16 mg on cycle 1, day 1; 0.8 mg on cycle 1, day 8; 3 mg on cycle 1, day 15; followed by the first full dose of 48 mg on cycle 1, day 22. Here, the data cutoff date was May 28, 2024, and the median follow-up was 2.9 months.

To be eligible for enrollment, patients must have had CD20-positive relapsed or refractory CLL, received at least two prior lines of systemic therapy and had an ECOG performance status of 0 to 2. No prior allogeneic hematopoietic cell transplant was permitted.

The primary end point in the expansion cohort was ORR; in the C1 OPT cohort, this was incidence and severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and clinical tumor lysis syndrome (CTLS). Key secondary end points in the expansion cohort included CR rate, time to response, minimal residual disease (MRD), and safety and tolerability.

In the expansion and C1 OPT cohorts, respectively, the median age was 72 years and 68 years; 74% and 82% of patients were male. The median time from initial diagnosis to first dose was 13 and 11 years, respectively. The median number of prior lines of therapy was four in both treatment groups; 61% and 53% received at least four prior lines of therapy. The median time from the last treatment to the first dose was 0.7 months and 1.6 months, respectively. All patients in both groups previously received a BTK inhibitor; 83% and 88% of patients had received a BCL-2 inhibitor.

Further efficacy findings showed that, in the response-evaluable group of the expansion cohort, the partial response (PR) rate was 24%, the stable disease (SD) rate was 19%, and 5% of patients had progressive disease (PD). In those with TP53 aberrations, these rates were 33%, 13%, and 7%. In patients with IGHV-unmutated disease, the rates were 19%, 19%, and 0%, respectively. In the double-exposed subgroup, these rates were 16%, 21%, and 5%, respectively.

In the C1 OPT cohort, the PR, SD, and PD rates were 50%, 20%, and 10%, respectively.

In the expansion cohort, the median time to response was two months, and the median time to CR was 5.6 months. The estimated one-year progression-free survival (PFS) and overall survival (OS) rates were 52% and 70%, respectively. The median PFS was 12.8 months, and the median OS was not reached. When an OS is not reached, it means the average amount of patients did not die at the time of data collection.

Danilov noted that, in the C1 OPT cohort, the rate and severity of CRS were reduced, and there were no cases of ICANS or CTLS. Here, the overall CRS rate was 82% and was grade 1 (mild), 2 (serious) and 3 in 71%, 12%, and 0% of patients. In the expansion cohort, the CRS rate was 96% and was grade 1, 2, and 3 in 9%, 70% and 17% of patients, respectively.

Actemra (tocilizumab; a treatment for CRS) was given in 91% and 43% of patients in the expansion and C1 OPT cohorts, respectively. No such events led to treatment discontinuation, and all CRS cases were resolved in both cohorts. The median time to resolution was three days in the expansion cohort and 3.5 days in the C1 OPT cohort.

In the expansion cohort, ICANS occurred in 13% of patients and were either grade 1 (4%) or 2 (9%); there was one case of CTLS, which was grade 2.

CRS events were also evaluated by dosing period. In the expansion cohort, these occurred at the first step-up dose (grade 1, 13%; grade 2, 21.7%), second step-up dose (grade 1, 36.4%; grade 2 13.6%), first full dose (grade 1, 18.2%; grade 2, 63.6%; grade 3, 18.2%); second full dose (grade 1, 10.5%; grade 2, 21.1%) and third full dose (grade 1, 6.3%; grade 2, 18.8%).

In the C1 OPT cohort, these also occurred at the first step-up dose (grade 1, 23.5%), second step-up dose (grade 1, 12.5%; grade 2, 6.3%), third step-up dose (grade 1, 31.3%), first full dose (grade 1, 46.7%; grade 2, 13.3%) second full dose (grade 1, 30.8%; grade 2, 7.7%) and third full dose (33.3%).

The phase 1/2 EPCORE CLL-1 trial is evaluating single-agent Epkinly and as a combination regimen with various agents in patients with CLL and Richter’s transformation. It is currently recruiting patients.

“Epcoritamab monotherapy in patients (Pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL): results from CLL expansion and optimization cohorts of Epcore CLL-1” by Dr. Alexey Danilov, et al. Presented at: 2024 ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 883.

Epkinly (epcoritamab-bysp) monotherapy demonstrated significant efficacy in heavily pretreated chronic lymphocytic leukemia (CLL) patients, as evidenced by the EPCORE CLL-1 trial. The expansion cohort showed a 67% overall response rate (ORR) and a 43% complete response (CR) rate, with notable responses in patients with TP53 aberrations and IGHV-unmutated disease. The cycle 1 optimization (C1 OPT) cohort had a 60% ORR. The trial highlighted reduced cytokine release syndrome (CRS) severity with optimized dosing and prophylaxis. The study continues to explore Epkinly's potential in CLL and Richter’s transformation.

Among patients with heavily pretreated chronic lymphocytic leukemia, treatment with Epkinly monotherapy showed deep responses.

Epkinly Leads to Responses in Heavily Pretreated Patients With CLL

Consolidative autologous hematopoietic cell transplant plus Rituxan versus Rituxan alone did not show a significant difference in survival among certain patients with mantle cell lymphoma. 

Patients with mantle cell lymphoma (MCL) did not demonstrate improved survival outcomes in a phase 3 study after receiving consolidative autologous hematopoietic cell transplant (auto-HCT) with Rituxan (rituximab) in their first complete remission (CR) with undetectable minimal residual disease (MRD).

Data from an analysis of the phase 3 ECOG-ACRIN EA4151/BMT-CTN 1601 trial was presented during the 

Between August 2017 and July 15, 2024, 650 patients were enrolled in the study. Patients who had an MRD-negative CR underwent randomization to auto-HCT plus Rituxan for three years (group A; 257 patients), or Rituxan alone for three years (group B; 259 patients). Those who had a partial response (MRD-positive or -negative) or an MRD-positive CR went onto the registration cohort (not randomly assigned) and received autoHCT plus Rituxan for three years (group C; 49 patients); those who had been deemed MRD indeterminate also had autoHCT plus Rituxan for three years (group D; 85 patients).

Autologous hematopoietic cell transplant (auto-HCT): collecting a patient’s healthy stem cells before treatment and returning the healthy cells to them after cancer treatment.

Complete remission: patients no longer show signs or symptoms of cancer.

Minimal-residual disease (MRD): microscopic traces of cancer cells that remain in the body.

Overall survival (OS): time patients live with cancer, regardless of their disease status, until death of any cause.

Progression-free survival (PFS): time patients live without their cancer worsening or spreading.

The primary analysis population included all randomized patients, but a treated-as-assigned analysis was also conducted because 25.3% of patients in group A and 0.8% in group B refused their assigned treatment.

The study showed that in all randomized patients, the three-year overall survival (OS) rate was 82.1% for auto-HCT plus Rituxan compared with 82.7% in the Rituxan-alone group; these rates were 86.2% versus 84.8% in the treated-as-assigned group.

“This means that the probability of detecting significant difference, even when the study is more fully read out, is highly improbable,” lead study author Dr. Timothy Fenske, a medical oncologist at Medical College of Wisconsin, said in an oral presentation during the meeting. “In this initial analysis, in the era of highly effective induction and maintenance regimens, [patients with] mantle cell lymphoma in first complete response with undetectable MRD did not benefit from consolidative autologous transplant. Longer follow-up will be important to confirm these findings.”

To be eligible for study enrollment, patients with MCL must have been between the ages of 18 and 70 years and in first remission. Rituxan-containing induction regimens were allowed and included those with BTK inhibitors.

Patients could be enrolled on the study before, during or after induction therapies. If clonal markers were present in molecular testing, patients went to post-induction restaging and submission of blood for MRD assessment; if no markers were found, they were identified as MRD indeterminate.

The primary end point was OS between the auto-HCT plus maintenance Rituxan versus maintenance Rituxan alone. Secondary measures included progression-free survival (PFS) in group A versus group B, as well as PFS in groups C and D and conversion rate of MRD-positive patients in group C to undetectable MRD following auto-HCT.

Study investigators assumed a six-year OS rate of 76% in the standard Rituxan maintenance group and targeted to detect a 10% improvement to 86% at six years when auto-HCT was added.

Findings from the study also showed that there was no significant difference observed in PFS outcomes between groups A and B. Three-year PFS rates in the all-randomized group were 76.6% and 77.4% for groups A and B, respectively; these rates were 81.5% and 80.4%, respectively, in the treated-as-assigned group.

When OS was measured between groups A and B comparing induction therapy intensity, it was found that the three-year OS rates were 83.0% for group A versus 86.2% for group B. In the non-intensive induction group, the three-year OS rates were 79.5% versus 72.8%, respectively.

“As we might expect, the survival appears somewhat superior in patients receiving intensive induction,” Fenske said. “However, receipt of autologous transplant was not associated with a significant improvement in overall survival regardless of induction intensity.”

OS was also evaluated in patients who were enrolled in groups C and D. Here, the three-year OS rates were 81.9% and 85.1%, respectively. Three-year PFS rates were 76.9% and 73.4%, respectively.

Study investigators conducted an exploratory analysis of the MRD-positive patients that comprised group C of posttransplant MRD status. The three-year PFS rates were similar at 100% versus 48.8%, respectively, “suggesting that MRD-positive patients may still benefit from autologous transplant,” Fenske said, and noted the small subgroup size.

Thirty-four deaths were reported on study, occurring from lymphoma (group A, 4.7%; group B, 3.5%; group C, 2.0%; group D, 2.4%), COVID-19 (5.1%; 6.6%; 2.0%; 3.5%), other (3.5%; 3.1%; 6.1%; 5.8%) and unknown causes (1.6%; 1.5%; 2.0%; N/A).

“Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial” by Dr. Timothy Fenske. 

A phase 3 study evaluated the impact of consolidative autologous hematopoietic cell transplant (auto-HCT) with Rituxan in mantle cell lymphoma (MCL) patients in first complete remission with undetectable minimal residual disease. The study found no significant improvement in overall survival (OS) or progression-free survival (PFS) for patients receiving auto-HCT plus Rituxan compared to Rituxan alone. The three-year OS rates were similar across treatment groups, and the study suggests that auto-HCT may not provide additional benefit in this patient population.

Autologous stem cell transplant plus Rituxan did not improve survival outcomes in certain patients with mantle cell lymphoma compared with Rituxan alone.

Survival Outcomes Not Improved With Autologous Stem Cell Transplant in MCL

Blenrep in combination with Velcade and dexamethasone improved survival and response rates compared to Darzalex in patients with relapsed or refractory multiple myeloma.

Patients with relapsed/refractory multiple myeloma experienced significant improvements in overall survival (OS) when treated with Blenrep (belantamab mafodotin) in combination with Velcade (bortezomib) and dexamethasone (BVd) versus those treated with Darzalex (daratumumab) plus Velcade and dexamethasone (DVd), trial results have shown.

Updated data from the phase 3 DREAMM-7 trial was presented during the 2024 ASH Annual Meeting and Exposition.

At a median follow-up of 39.4 months, the median OS was not reached (NR) in both the BVd (243 patients) and DVd (251 patients) arms. The predicted median OS based on modeling is 84 months with BVd versus 51 months with DVd. The estimated 24-month survival rates in the respective arms were 79% and 67%; these respective rates at 36 months are 74% and 60%.

Moreover, deeper responses were achieved and maintained with Blenrep vs Darzalex. The objective response rate (ORR) with BVd was 83.1% versus 71.3% with DVd. The median duration of response (DOR) with BVd was more than double that achieved with DVd, at 40.8 months and 17.8 months, respectively.

The percentage of those who achieved a complete response or better and minimal residual disease (MRD) negativity with a sensitivity of 10

 was 25.1% in the BVd arm versus 10.4% in the DVd arm. The percentage of patients who experienced a very good partial response or better and MRD negativity with a sensitivity of 10

 in the respective arms was 38.7% and 17.9%, respectively.

Overall survival (OS): the time a patient lives, regardless of disease status.
Objective response rate (ORR): patients who respond partially or completely to treatment.

Duration of response (DOR): the length of time a patient responds to treatment.
Complete response (CR): the disappearance of cancer.

Minimal residual disease (MRD): small amounts of remaining cancer cells.

Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.

Treatment benefit derived with BVd was also maintained after subsequent antimyeloma therapy. The median time to second objective disease progression (PFS2) with BVd was NR versus 33.4 months with DVd.

“BVd demonstrated an early, sustained and statistically significant OS benefit in a head-to-head trial against the [Darzalex] combination,” Dr. Vania Hungria of Clinica Sao Germano, in Sao Paulo, Brazil, said in a presentation of the data. “DREAMM-7 has now shown statistically significant [progression-free survival (PFS)], OS, DOR and MRD negativity benefits compared with DVd. [As such,] these results further support the use of BVd as a potential new standard of care in relapsed or refractory multiple myeloma.”

The randomized, open-label, phase 3 DREAMM-7 study enrolled patients with multiple myeloma who were at least 18 years of age and received at least one prior line of therapy and experienced documented progressive disease (PD) after their most recent line. Patients could not have previous exposure to anti-BCMA therapy, nor could they have disease that was refractory to or intolerant of Darzalex or Velcade.

Participants were randomly evenly assigned to receive Blenrep at a dose of 2.5 milligrams per kilogram (mg/kg) intravenously (IV) every three weeks paired with Velcade and dexamethasone versus Darzalex at a dose of 16 mg/kg IV weekly for cycles 1 to 3 and then every three weeks for cycles 4 to 8. For cycles 9 and later, those in the investigative and control arms received single-agent Blenrep at 2.5 mg/kg IV every three weeks or Darzalex monotherapy at 16 mg/kg IV every four weeks, respectively. Treatment continued until the study concluded, consent was withdrawn, PD, death or intolerable toxicity.

PFS served as the trial’s primary end point, and at a median follow-up of 28.2 months this was met. The median PFS of 36.6 months with BVd versus 13.4 months with DVd translated to a 59% reduction in the risk of disease progression or death. At the time of the primary analysis, median OS was NR in both arms, but a strong trend favored the BVd regimen. In November 2024, the FDA accepted a biologics license application seeking the approval of BVd in patients with multiple myeloma who have received at least 1 prior therapy based on DREAMM-7 data. The target action date is July 23, 2025.

Key secondary end points of the trial included OS, DOR and MRD. End points were tested in the following hierarchy: PFS, followed by OS and DOR, followed by MRD. Additional secondary end points of interest included CR rate, ORR, clinical benefit rate, time to response, time to progression, PFS2 and adverse effects (side effects), particularly ocular findings.

Of the total 494 patients enrolled, 243 were assigned to the BVd arm and 251 were assigned to the DVd arm; 242 and 246 patients, respectively, received treatment. A higher percentage of patients on the BVd arm remained on therapy versus those on the DVd arm, at 25% and 15%, respectively. The most common reason for discontinuation in the BVd arm was PD (30%), followed by toxicity (21%), physician decision (13%), patient withdrawal (10%), loss to follow-up (less than 1%) and protocol-defined stopping criteria reached (less than 1%).

The data cutoff date of the analysis shared during the meeting was Oct. 7, 2024. At this time point, the median duration of exposure to BVd was 15.9 months versus 12.8 months in the DVd arm. Baseline characteristics and prior treatments received proved to be balanced across the arms, according to Hungria, who added that approximately half of patients received one prior line of therapy.

“More patients in the DVd group discontinued treatment early due to progression and went on to receive a subsequent antimyeloma therapy,” Hungria said. “The most common subsequent therapy in both arms include immunomodulatory drugs like [Revlimid (lenalidomide)] and [Pomalyst (pomalidomide)]. Of patients who received subsequent therapies, more than half received anti-CD38 monoclonal antibodies immediately after BVd, and [Kyprolis (carfilzomib)] was given often after DVd.”

Regarding safety, any-grade side effects (AEs) occurred in all patients in the BVd and DVd arms; these effects were related to study treatment for 100% and 95% of patients, respectively. Grade 3 (severe) or 4 (life-threatening) AEs occurred in 95% and 78% of patients, respectively, with 92% and 67% related to study treatment. In the BVd arm, AEs led to dose delays or reductions for 95% and 75% of patients, respectively; in the DVd arm, these rates were 76% and 59%. AEs resulted in permanent discontinuation of treatment for 32% of those given BVd and 19% of those who received DVd. Serious AEs related to any study treatment were experienced by 21% and 13% of patients and serious AEs proved to be fatal for 11% and 8% of patients.

“AEs were consistent with the known safety profile for the individual agents in each regimen,” Hungria noted. “Although the BVd arm had numerically higher overall rates of grade 3 or 4 and serious AEs, when adjusting for total treatment exposure, safety results were generally comparable between arms. There were more deaths due to myeloma in the DVd vs the BVd arm.”

She added that thrombocytopenia was more common in the BVd arm, even when adjusted for exposure. Overall, infection rates were similar between the arms and consistent with the primary analysis. In the BVd and DVd arms, exposure-adjusted rates of infections per 100 person-years were 43.75% and 48.71% for all-grade events, and 19.89% versus 14.29%, respectively, for grade 3 or higher events.

“About two-thirds of patients did not have a clinically meaningful drop in best-corrected visual acuity, [BCVA]” Hungria said. “Overall, the ocular safety profile is consistent with the primary analysis. Nearly all patients with worsening of vision to 20/50 had resolution to normal baseline or improvement of the first event. The 2% of patients with an ongoing event had insubstantial follow-up to assess for resolution.” In the BVd arm, blurred vision was the most frequent ocular event experienced; 68% experienced an any-grade event and 24% experienced a grade 3 or 4 event. Ten percent of patients discontinued due to an ocular event.

“The interval between doses increased with time due to dose modification, from initial three weeks up to 12 weeks,” Hungria noted. “Despite the extended dose intervals, the responses were maintained.” Twenty-three percent of patients experienced 20/50 or worse ocular events in the first three months and prevalence generally dropped thereafter. Notably, the rate of treatment discontinuation due to these events was low, she concluded.

Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma: overall survival analysis and updated efficacy outcomes of the phase 3 DREAMM-7 trial” by Dr. Vania Hungria et al., 

Patients with relapsed/refractory multiple myeloma showed improved overall survival (OS) with Blenrep (belantamab mafodotin) combined with Velcade (bortezomib) and dexamethasone (BVd) compared to Darzalex (daratumumab) with Velcade and dexamethasone (DVd). The phase 3 DREAMM-7 trial indicated a predicted median OS of 84 months for BVd versus 51 months for DVd. BVd also demonstrated superior objective response rate (ORR), duration of response (DOR), and minimal residual disease (MRD) negativity. Safety profiles were consistent, though BVd had higher rates of grade 3/4 adverse events.

Gina Mauro

Real-World Data May Confirm Monjuvi’s Efficacy in Large B-Cell Lymphoma

Epkinly Leads to Responses in Heavily Pretreated Patients With CLL

Survival Outcomes Not Improved With Autologous Stem Cell Transplant in MCL

Blenrep Combo Improves Survival in Relapsed/Refractory Multiple Myeloma

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