Kristie L. Kahl is vice president of content at MJH Life Sciences, overseeing CURE®, CancerNetwork®, the journal ONCOLOGY, Targeted Oncology, and Urology Times®. She has been with the company since November 2017.

She is a graduate of Rider University, where she acquired a Bachelors of Art in journalism, as well as a graduate of Temple University, where she received her Masters of Science in Sports Management.

Follow Kristie on Twitter at @KristieLKahl, or email her at kkahl@mjhlifesciences.com.

Kristie L. Kahl

A treatment combination called D-VRd showed improvements in minimal-residual disease responses in certain patients with newly diagnosed multiple myeloma. 

In patients with transplant-ineligible or -deferred newly diagnosed multiple myeloma, adding Darzalex (daratumumab) to Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (VRd) demonstrated improved minimal-residual disease (MRD) responses.

These findings were based on an analysis of MRD outcomes from the phase 3 CEPHEUS trial, presented at the 

In addition, the combination led to improved progression-free survival (PFS), regardless of MRD negative or positive status.

Minimal-residual disease (MRD): microscopic traces of cancer that remain in the body after receiving treatment. MRD-negativity means there are no detectable traces of cancer in the body.

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

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

Partial response (PR): patients respond to treatment but not completely, meaning their tumors shrunk after receiving treatment.

End point: the main goal of a study measured at the end to see if the treatment worked.

Subcutaneous: treatment given beneath the skin.

ECOG performance status: a measurement of how independently patients can complete daily tasks. A score of 0 means patients can perform tasks fully independently and a score of 4 means they cannot perform tasks independently.

“These data support the use of [Darzalex] in combination with VRd as a normal standard of care in patients with newly diagnosed multiple myeloma who are transplant ineligible or when transplant is deferred,” Dr. Sonja Zweegman from the Department of Hematology at Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Netherlands, said during a presentation of the data.

After a median follow-up of 58.7 months, at a 10

sensitivity, the overall MRD-negativity rate was 60.9% for patients treated with Darzalex plus VRd (197 patients) versus 39.4% for those given VRd alone (198 patients). At a 10

 sensitivity, the overall MRD-negativity rates were 46.2% for patients in the daratumumab plus VRd group versus 27.3% for the VRd group.

“It can be appreciated … that adding [Darzalex] to VRd led to a 50% increase in MRD negativity,” Zweegman said.

The 54-month PFS rates were 68.1% and 49.5%, respectively, reducing the risk for disease progression or death by 43%. Zweegman noted that the MRD negativity rates were generally consistent across prespecified subgroups.

When evaluating cumulative MRD negative complete response (CR) rates from the sensitivity level 10

, patients reached MRD negativity faster, with higher rates at all time points. “And the difference of the MRD negativity rates between the [two treatment groups] is increasing up to three years,” Zweegman added.

This same effect was seen at the sensitivity level 10

, which is even more related to PFS, she noted. “And importantly… [Darzalex] almost doubles the MRD negative CR rates that sustained for more than 12, 24 and 36 months.”

, MRD-negative patients experienced superior PFS, compared with MRD-positive patients in both treatment groups. Further, the 54-month PFS rates for MRD-negative patients treated with Darzalex plus VRd or VRd alone were 86.2% and 79.0%, respectively. In MRD-positive patients, these rates were 51% and 36.5%.

“So [Darzalex] provides PFS benefit regardless of the MRD negativity CR status,” Zweegman said.

The CR or better rate was 81.2% in the Darzalex group versus 61.6% in the VRd group. In the Darzalex plus VRd group, the stringent CR, CR, very good partial response (PR), and PR rates were 65.0%, 16.2%, 11.7% and 4.1%, respectively. In the VRd group, these respective rates were 44.4%, 17.2%, 25.3% and 6.1%.

Regarding safety, grade 3 or 4 (severe or life-threatening) treatment-emergent side effects occurred in 92.4% of patients in the Darzalex group versus 85.6% of patients in the VRd group. Treatment-emergent side effects led to discontinuation of all study drugs in 7.6% and 15.9% of patients, respectively.

The most common any-grade treatment-emergent side effects included blood and lymphatic disorders (Darzalex group, 82.7%; VRd group, 64.6%), including neutropenia (55.8%; 39.0%), thrombocytopenia (46.7%; 33.8%) and anemia (37.1%; 31.8%). Gastrointestinal disorders occurred (79.7%; 81.5%), including diarrhea (56.9%; 59%) and constipation (38.1%; 42.1%); general disorders and administration-site conditions (80.7%; 75.4%), including peripheral edema (42.1%; 39%) and fatigue (32%; 30.8%). Psychiatric disorders occurred (46.2%; 49.2%), including insomnia (32%; 32.3%); infections (91.9%; 85.6%), including upper respiratory tract infection (39.6%; 32.8%) and COVID-19 (38.1%; 24.6%); and second primary malignancies (7.6%; 9.2%).

More About MRD-Negativity in Multiple Myeloma

“We all know that MRD negativity is associated with longer survival, and it's a strong prognostic for clinical end points in multiple myeloma and a key goal of multiple myeloma therapy,” Zweegman explained. “And therefore, MRD negativity was supported by the [FDA Oncologic Drugs Advisory Committee] as an early end point for accelerated approval in multiple myeloma.”

The phase 3 CEPHEUS trial was the first phase 3 study of Darzalex with MRD as a primary end point. In the trial, investigators demonstrated that the addition of subcutaneous Darzalex with VRd in patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma led to superior rates of overall and sustained MRD negativity, as well as more CR, and it significantly improved PFS.

At the 2024 ASH Annual Meeting, Zweegman reported on an expanded analysis of MRD outcomes from the CEPHEUS trial.

In the trial, investigators randomly assigned patients evenly to receive Darzalex at 1,800 milligrams (mg) once per week, then once every three weeks, plus 1.3 mg per square meter of Velcade; 25 mg of Revlimid and 20 mg of dexamethasone; or VRd alone at the same dosing schedule. Starting in cycle 9, patients in the experimental group received 1,800 mg of Darzalex once every 4 weeks plus 25 mg of Revlimid and 40 mg of dexamethasone; patients in the control group received Rd at the same dosing schedule.

The overall MRD-negativity rate with a CR or better served as the trial’s primary end point. Secondary end points included PFS; the proportion of patients with sustained MRD negativity with a CR or better for at least 12 months; and CR or better rate.

Patients were required to have an ECOG performance status (PS) of 0 to 2 and a frailty score of 0 or 1.

“Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma or for Whom Transplant Is Not Planned As Initial Therapy: Analysis of Minimal Residual Disease in the Cepheus Trial” by Dr. Sonja Zweegman, et al. Presented at: 2024 ASH Annual Meeting; December 7-10, 2024; San Diego, California.

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Articles

The addition of Darzalex (daratumumab) to the VRd regimen (Velcade, Revlimid, and dexamethasone) in transplant-ineligible or deferred newly diagnosed multiple myeloma patients significantly improved minimal-residual disease (MRD) negativity and progression-free survival (PFS). The phase 3 CEPHEUS trial demonstrated a 50% increase in MRD negativity with Darzalex, with consistent benefits across subgroups. Despite higher rates of severe side effects, the combination therapy showed superior MRD-negative complete response rates and PFS, supporting its use as a standard care option for this patient population.

Patients newly diagnosed with multiple myeloma who are transplant ineligible or deferred may benefit from receiving a Darzalex treatment combination. 

Darzalex Regimen May Improve MRD Responses in Multiple Myeloma

Darzalex Faspro showed improved survival outcomes in patients with smoldering multiple myeloma compared with active monitoring. 

Patients with intermediate- or high-risk smoldering multiple myeloma experienced benefits in progression and survival following treatment with subcutaneous Darzalex Faspro (daratumumab) when compared with active monitoring, study results have shown.

Primary results from the phase 3 AQUILA study were presented at the 

Additionally, the greatest benefit was seen among patients with high-risk disease.

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

Overall survival (OS): the time a patient lives, regardless of disease status.

Overall response rate (ORR): patients who responded partially or completely to treatment.

“We believe that with these data, patients with high-risk smoldering myeloma may benefit from immediate treatment with [Darzalex Faspro], and that observation for this particular subset of patients may not be an adequate option,” Dr. Meletios-Athanasios Dimopoulos, professor and chairman, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra General Hospital, in Athens, Greece, said during a press briefing at the meeting.

After a median follow-up of 65.2 months, the median progression-free survival (PFS) was not reached (NR) with Darzalex Faspro monotherapy compared with 41.5 months with active monitoring. Further, 60-month PFS rates were 63.1% and 40.8%, respectively, reducing the risk for disease progression or death by 51% with subcutaneous Darzalex Faspro.

“Furthermore, there were fewer patients in the [Darzalex Faspro] arm who progressed with CRAB criteria [12 versus 34, respectively] and with SLiM criteria [50 versus 65]. So not only [did Darzalex Faspro delay] progression, but [patients who received this agent] also avoided a clinically obvious and important type of progression,” Dimopoulos explained.

In total, 15 patients in the Darzalex Faspro arm (7.7%) and 26 patients in the active monitoring arm (13.3%) died. The 60-month overall survival (OS) rates were 93% with Darzalex Faspro compared with 86.9% with active monitoring, reducing the risk for death by 48%. “The majority of deaths were due either to progressive disease during or after the study,” Dimopoulos added.

In addition, Darzalex Faspro monotherapy demonstrated a superior overall response rate (ORR) of 63.4% compared with 2% with active monitoring, with an improved median time to first-line treatment for active myeloma (NR versus 50.2 months, respectively).

Grade 3 (severe) or higher treatment-emergent side effects occurred in 40.4% of patients in the Darzalex Faspro arm compared with 30.1% of those undergoing active monitoring, with the most common being hypertension (5.7% versus 4.6%, respectively). The most common serious treatment-emergent side effect was pneumonia (3.6% versus 0.5%, respectively).

“There were no new safety signals from what we know,” Dimopoulos said. “There was somehow an increased risk of infection, but these were well treated and reversible.”

Eleven patients discontinued Darzalex Faspro treatment due to treatment-emergent side effects, whereas 90 patients underwent dose modifications as a result.

Although observation is the current standard of care for this patient population, Dimopoulos suggested that therapeutic intervention may benefit patients with high-risk disease.

At the meeting, Dimopoulos presented on the primary analysis results from the phase 3 AQUILA study after 36 months of Darzalex Faspro monotherapy compared with active monitoring, aimed at assessing the effect of early intervention to prevent end-organ damage and progression to active disease.

“This is the largest phase 3 trial conducted in patients with high-risk smoldering myeloma,” Dimopoulos noted.

In the open-label, multicenter, randomized phase 3 trial, investigators randomly assigned patients to receive either subcutaneous Darzalex Faspro monotherapy (194 patients) or active monitoring (196 patients) for 36 months or until confirmation of disease progression, whichever occurred first. 

Following treatment, patients underwent efficacy follow-up until progression by SLiM-CRAB criteria, with survival follow-up conducted every six months until the end of the study.

Patients were enrolled at 124 sites across 23 countries between Dec. 10, 2017, and May 27, 2019.

The median age was 64 years, and 40.5% of patients were classified as having high-risk disease in accordance with the Mayo 2018 risk criteria. The median time from initial diagnosis of smoldering myeloma to randomization was 0.74 years.

By the clinical cutoff (May 1, 2024), 65.5% and 40.8% of patients in the Darzalex Faspro and active monitoring arms, respectively, completed 36 months of treatment. The most common reason for treatment discontinuation across both arms was progressive disease (21.8% versus 41.8%, respectively).

In November 2024, a supplemental biologics license application was submitted to the FDA, and an extension of indication application was submitted to the European Medicines Agency, for subcutaneous Darzalex Faspro to treat adult patients with high-risk smoldering multiple myeloma based on results from this trial.

“I believe it is important to have an approved therapy, and then based on the practice of the physician and the patient they can make a joint decision whether [the patient] will get the treatment,” Dimopoulos said.

“Phase 3 Randomized study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the Aquila study” by Dr. Meletios-Athanasios Dimopoulos et al., 

Subcutaneous Darzalex Faspro (daratumumab) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with intermediate- or high-risk smoldering multiple myeloma compared to active monitoring. The phase 3 AQUILA study demonstrated a 51% reduction in disease progression or death risk and a 48% reduction in death risk with Darzalex Faspro. The treatment showed a superior overall response rate and delayed progression to active myeloma. Despite increased treatment-emergent side effects, the benefits suggest therapeutic intervention for high-risk patients may be advantageous.

The risk for disease progression or death was reduced by 51% with subcutaneous Darzalex Faspro in certain patients with smoldering multiple myeloma.

Darzalex Faspro May Improve Progression, Survival in Smoldering Multiple Myeloma

Combining Calquence and Venclexta, with or without Gazyva, significantly improved progression-free survival for patients with untreated chronic lymphocytic leukemia, regardless of their IGHV mutational status, compared to standard chemotherapy and immunotherapy.

Combining Calquence (acalabrutinib) with Venclexta (venetoclax), with or without Gazyva (obinutuzumab), significantly increased progression-free survival for patients with untreated chronic lymphocytic leukemia (CLL), regardless of their IGHV mutational status, compared to standard chemotherapy and immunotherapy, according to data from a phase 3 trial presented at the 2024 ASH Annual Meeting.

At a median follow-up of 40.8 months, the median progression-free survival (PFS) was not reached with Calquence plus Venclexta (AV) and Calquence plus Venclexta and Gazyva (AVO) groups, and was 47.6 months with investigator’s choice of fludarabine plus cyclophosphamide and Rituxan (rituximab; FCR) or bendamustine plus Rituxan (BR). Treatment with the doublet regimen reduced the risk of disease progression or death by 35% and the triplet reduced this risk by 58%. The estimated 36-month PFS rates with Calquence plus Venclexta, with or without Gazyva, respectively, were 83.1% and 76.5%, compared with 66.5% with standard-of-care (SOC) chemoimmunotherapy.

Atrial fibrillation: a heart rhythm disorder where the upper chambers of the heart (atria) beat irregularly.

ECOG performance status of 2 or lower: a measure of a patient's functional ability and how well they can perform daily activities. A lower score indicates better functional status.

Progression-free survival: the length of time a patient lives without disease worsening.

Cumulative Illness Rating Scale-Geriatric of over 6: a scale used to assess the overall health and frailty of older adults. A higher score indicates more significant health problems.

“AMPLIFY provides the first phase 3 evidence of fixed duration therapy with a combination of [Venclexta] and a second generation BTK inhibitor in patients with treatment-naive CLL,” Dr. Jennifer R. Brown, director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School in Boston, said during a press briefing at the meeting.

The phase 3 AMPLIFY study enrolled patients with treatment-naive CLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia 2018 criteria who are at least 18 years of age and whose tumors are without del(17p) or TP53 mutations. Patients were required to have an ECOG performance status of 2 or lower. Patients were excluded from the trial if they had a Cumulative Illness Rating Scale-Geriatric of over 6 or if they had significant cardiovascular disease.

A total of 867 patients were randomized evenly to receive one of the following regimens:

Oral Calquence at 100 milligrams (mg) twice daily for cycles 1 to 14 plus oral Venclexta daily with a five-week dose ramp-up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg for cycles 3 to 14

The same Calquence and Venclexta dosing plus intravenous Gazyva at 1000 mg for days 1, 8 and 15 of cycle 2 and day 1 of cycles 3 to 7

Investigator’s choice of FCR or BR per standard dosing protocol for cycles 1 to 6

Additional efficacy findings showed that PFS was improved with Calquence plus Venclexta, with or without Gazyva, regardless of IGHV status.

“Particularly noticeable is the fact that in the [triplet] group, those patients with unmutated IGHV [36-month PFS rate, 82.8%] are doing as well as those with mutated IGHV [36-month PFS rate, 83.6%], suggesting that the addition of [Gazyva] may overcome the adverse impact of unmutated IGHV,” Brown explained.

Further, investigators found the highest rate of undetectable minimal residual disease (uMRD) among those who received the regimen with Gazyva. Of the patients who were evaluable at end of therapy, uMRD rates at a sensitivity level 10

 in the peripheral blood were 45% in the doublet group, 95% in the triplet group and 72.9% in the investigators’ choice group.

The 36-month OS rates with the doublet, triplet, and FCR/BR regimens were 94.1%, 87.7% and 85.9%, respectively. “Of note, the study was conducted at the height of the pandemic, and COVID-19 deaths were seen in 10 patients on the [doublet] group, 25 on the [triplet] group and 21 on the chemoimmunotherapy group,” Brown explained. Therefore, after pre-planned censoring, the adjusted rates were 97.5%, 96.2% and 93.7%, respectively.

The most common grade 3 (severe) or worse side effect (AE) was neutropenia, low white blood cell count, occurring in 26.8% of those who received the AV regimen (291 patients), 35.2% of those given AVO (284 patients) and 32.4% of those given FCR/BR (259 patients). Serious AEs were seen in 24.7%, 38.4% and 27.4% of patients, respectively.

Patients with treatment-naive CLL have a variety of options, such as a fixed-duration regimen of Venclexta and Imbruvica (ibrutinib); however, Brown noted that despite deep and durable responses, cardiac toxicity remains. When evaluating AEs of interest, 9.3% and 12% of patients in the doublet and triplet groups experienced a cardiac event, compared with 3.5% of those in the FCR/BR group; grade 3 or worse cardiac events occurred in 1.7%, 2.5% and 1.2% of patients, respectively. However, rates of grade 3 or worse atrial fibrillation (0.3% versus 0.7% versus 0.8%, respectively) and hypertension (2.7% versus 2.1% versus 0.7%) remained low.

Of note, Brown acknowledged that the study was limited by the control group treatment regimen no longer being considered the SOC, which occurred after the trial began in 2019. “I think when physicians are considering whether to use the two or the three-drug regimen, they have to take account of the patient in front of them,” she concluded.

“Based on these impressive data from the AMPLIFY trial, Calquence is only the second-generation BTK inhibitor to demonstrate efficacy in the front-line treatment of patients with chronic lymphocytic leukemia as both a treat-to-progression and a fixed-duration approach,” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, stated in a press release on the data. “This advance is an important development for patients and their physicians who seek new options and more flexibility in managing this disease in the long term.”

“Fixed-duration Calquence plus Venclexta with or without Gazyva Versus chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia: interim analysis of the multicenter, open-label, randomized, phase 3 AMPLIFY trial.” By Dr. Jennifer R. Brown, et al., 

The combination of Calquence (acalabrutinib) and Venclexta (venetoclax), with or without Gazyva (obinutuzumab), significantly improved progression-free survival (PFS) in untreated chronic lymphocytic leukemia (CLL) patients compared to standard chemoimmunotherapy. The phase 3 AMPLIFY trial demonstrated that this regimen reduced the risk of disease progression or death, with notable efficacy regardless of IGHV mutational status. The study also highlighted the potential of the triplet regimen to overcome adverse impacts of unmutated IGHV. However, cardiac toxicity and neutropenia were observed as significant adverse events.

Calquence plus Venclexta, with or without Gazyva, improved progression-free survival over the standard-of-care chemoimmunotherapy in patients with untreated chronic lymphocytic leukemia.

Calquence Plus Venclexta Combo May Improve Survival in Frontline CLL

Revuforj showed continued effectiveness in treating patients with relapsed or refractory KMT2A acute leukemia, with high rates of minimal residual disease negativity and progression to stem cell transplant.

Patients with relapsed or refractory KMT2Ar acute leukemia continued to experience clinically meaningful responses, such as higher rates of minimal residual disease (MRD) negativity and the percentage of procession to hematopoietic stem cell transplant (HSCT) when treated with Revuforj (revumenib).

Updated analysis from the phase 2 AUGMENT-101 trial presented at the 2024 ASH Annual Meeting also showed that the safety profile of the agent continued to be manageable, with no patients discontinuing therapy due to differentiation syndrome or QTc prolongation.

“This trial represents the largest evaluation of a targeted therapy for patients with relapsed/refractory KMT2Ar acute leukemias to date, including the largest pediatric menin inhibitor cohort,” Dr. Ibrahim Aldoss, associate professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, said during a presentation of the longer follow-up. “…[Revuforj] is the first approved menin inhibitor and first approved treatment for KMT2Ar acute leukemia.”

Minimal residual disease (MRD) negativity: the absence of small amounts of cancer cells.

Hematopoietic stem cell transplant (HSCT): when healthy stem cells are infused into a patient.

Differentiation syndrome: a serious side effect caused by the large, rapid release of cytokines from leukemia cells affected by anticancer drugs, according to the National Cancer Institute.

QTc prolongation: when it takes longer than usual for the heart to recharge between beats, according to the Mayo Clinic.

Complete remission (CR): the disappearance of signs and symptoms of cancer.

Complete remission with partial hematologic recovery (CRh): when all signs of cancer have disappeared, but a patient’s blood cell counts have not returned to normal levels, according to The University of Texas MD Anderson Cancer Center.

Duration of response (DOR): how long a patient responds to treatment.

Febrile neutropenia: when a patient has a fever and a low count of white blood cells.

Anemia: a low count of healthy red blood cells.

As of the data cutoff of Feb. 29, 2024, the overall response rate (ORR) was 63.9%, including a complete remission (CR) or a CR with partial hematologic recovery (CRh) rate of 22.7% and composite CR (CRc) of 42.3%.

Of 18 CR+CRh responders and 36 CRc responders who were evaluable, 11 (61.1%) and 21 (58.3%), respectively, experienced MRD negativity.

Further, median duration of response (DOR) for the 22 CR+CRh responders was 6.4 months. In total, eight patients remain in follow-up without relapse or death. Aldoss noted that the updated median DOR of CR+CRh for the 13 patients who responded to Revuforj treatment in the interim analysis was 13 months.

The median time to first response in all responders was one month, and was two months in CR+CRh responders.

Overall, 21 patients (33.9%) in the ORR cohort went on to receive HSCT, of which nine (42.9%) of them restarted treatment with Revuforj after a median of 70 days. Of the patients who went on to receive HSCT, nine of the 11 CRc responders and four of the six CR or CRh responders with MRD status available were negative.

Grade 3 (severe) or higher treatment-emergent or treatment-related side effects occurred in 91.4% and 54.3% of patients, respectively, of which 77.6% and 36.2% were serious. Treatment-emergent side effects led to dose reduction in 9.5% of patients and discontinuation in 13.8% of patients, while treatment-related side effects led to reduction and discontinuation in 8.6% and 5.2%, respectively.

The most common grade 3 or higher treatment-emergent side effects were febrile neutropenia (38.8%), anemia (19.8%), decreased platelet count (16.4%), differentiation syndrome (14.7%), decreased neutrophil count (14.7%), decreased white blood cell count (14.7%), sepsis (13.8%) and QTc prolongation (12.9%). No new safety signals were reported and no patients discontinued treatment due to cytopenias, differentiation syndrome or QTc prolongation, Aldoss said.

Aldoss noted that treatments are needed for KMT2Ar acute leukemia, as many patients relapse after chemotherapy and/or HSCT, with remaining remission rates in both adults and pediatrics remaining low.

Therefore, in the phase 2 AUGMENT-101 trial, investigators evaluated the safety and efficacy of the oral, small molecule menin inhibitor.

Patients received 163 milligrams (mg) (95 mg per square meter) if body weight less than 40 kilograms) every 12 hours orally plus a strong CYP3A4 inhibitor in 28-day cycles until lack of at least morphological leukemia-free state after four cycles, disease progression or unacceptable side effects.

CR and CRh rates, as well as safety and tolerability served as the primary end points. Secondary end points included the rate of CRc (defined as CR plus CRh plus CR with incomplete platelet recovery plus CR with incomplete count recovery), ORR, DOR and time to response.

Patients were eligible with the following criteria: age of 30 days or more; relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, or mixed-phenotype acute leukemia with KMT2Ar or NPM1m; and patients with primary refractory or relapsed refractory disease. Patients were excluded if they had active central nervous system disease.

Among the patients in the efficacy (97 patients) and safety (116 patients) analyses, median age was 37 years and 35.5 years, respectively, with the majority of both groups being in the age range of 18 to 65 years (67% and 63.8%). Over half of both groups were women (56.7% and 57.8%, respectively) and were White (71.1% and 69%).

According to the abstract, patients underwent a median of two prior therapies, with 51 (44%) receiving three or more prior lines, 73 (63%) receiving prior Venclexta (venetoclax) and 59 (51%) who underwent prior HSCT.

Aldoss concluded by noting that the independent NPM1m cohort results from the trial will be presented in future publications.

“Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia” by Dr. Ibrahim Aldoss et al., presented at: 2024 ASH Annual Meeting; Dec. 7 to 10, 2024, San Diego, California, abstract 211.

Revuforj (revumenib) demonstrates promising efficacy and manageable safety in relapsed/refractory KMT2Ar acute leukemia, with significant MRD negativity and HSCT progression rates. The phase 2 AUGMENT-101 trial reports a 63.9% overall response rate, with a median duration of response of 6.4 months. Safety analysis reveals no new signals, with common severe side effects including febrile neutropenia and anemia. The trial underscores the unmet need for effective treatments in KMT2Ar acute leukemia, highlighting Revuforj as the first approved menin inhibitor for this condition.

Long-term follow-data shows Revuforj to be effective in the treatment patients with R/R KMT2Ar acute leukemias.

Kristie L. Kahl

Darzalex Regimen May Improve MRD Responses in Multiple Myeloma

Darzalex Faspro May Improve Progression, Survival in Smoldering Multiple Myeloma

Calquence Plus Venclexta Combo May Improve Survival in Frontline CLL

Revuforj Continues to Elicit Meaningful Responses in Some With Acute Leukemia

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