Roman Fabbricatore

Data from the AQUILA study support the use of fixed-duration subcutaneous Darzalex Faspro as an early treatment option in high-risk smoldering myeloma: © stock.adobe.com.

A poster presented at the 2025 Society of Hematologic Oncology Annual Meeting showed that subcutaneous Darzalex Faspro (daratumumab and hyaluronidase-fihj) significantly lowered the risk of disease progression or death compared with active monitoring in patients with high-risk smoldering multiple myeloma.

With a median follow-up of 65.2 months, the median progression-free survival (PFS) was not reached with Darzalex Faspro versus 41.5 months with monitoring, correlating with a 51% reduction in the risk of progressive disease or death. Per International Myeloma Working Group SLiM diagnostic criteria, investigators noted progression to multiple myeloma in 25.8% (50 of 194 patients) and 33.2% (65 of 196 patients) of each respective arm. Progression to multiple myeloma occurred in 6.2% (12 of 194 patients) and 17.3% (34 of 196 patients) of patients in each arm.

Investigators highlighted a PFS benefit with Darzalex Faspro across all pre-specified subgroups. An especially pronounced benefit occurred among patients with high-risk status; the median PFS was not reached with Darzalex Faspro versus 22.1 months with monitoring in this group.

“Darzalex Faspro demonstrated a favorable safety profile, with a low rate (5.7%) of treatment discontinuation due to treatment-emergent side effects. Patients maintained their health-related quality of life during Darzalex Faspro treatment compared with active monitoring,” lead study author, Dr. Meletios Athanasios Dimopoulos, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece, wrote in the poster with coauthors. “Results from the phase 3 AQUILA study strongly support early intervention with subcutaneous Darzalex Faspro monotherapy for a fixed duration in patients with high-risk smoldering multiple myeloma, representing an opportunity to delay or avoid end-organ damage and progression to multiple myeloma although preserving quality of life and extending survival.”

In the open-label, multicenter phase 3 AQUILA study, 390 patients were randomly assigned to receive subcutaneous Darzalex Faspro at 1800 milligrams every week on cycles 1 and 2, every two weeks on cycles 3 to 6, and every four weeks thereafter for a maximum of 36 months (194 patients) or active monitoring, which consisted of no disease-specific therapy with side effect monitoring for up to 36 months (196 patients). During the study’s follow-up phase, investigators evaluated efficacy until progression and assessed survival every 6 months until the study’s conclusion.

The trial’s primary end point was independent review committee. Key secondary end points included objective response rate (ORR), time to first-line treatment for multiple myeloma, PFS on first-line treatment, and overall survival (OS).

Patients 18 years and older with a confirmed smoldering multiple myeloma diagnosis per International Myeloma Working Group criteria for no longer than 5 years, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial.

The median age was 63 years in the Darzalex Faspro arm and 64.5 years in the active monitoring arm, and most from each respective arm were women (51% versus 52.6%). In each arm, most patients had an ECOG performance status of 0 (85.1% versus 81.6%), fewer than thre risk factors for progression to multiple myeloma (79.4% versus 79.6%), and intermediate-risk (39.7% versus 38.8%) or high-risk status (37.1% versus 43.9%).

Data showed an ORR of 63.4% with Darzalex Faspro versus 2% with active monitoring. Among patients who received Darzalex Faspro, a very good partial response or better occurred in 29.9%, and 8.8% had a complete response or better.

The median time to initiating subsequent frontline therapy was not reached in the Darzalex Faspro arm and 50.2 months in the monitoring arm. The 60-month PFS rate on frontline therapy was 85.9% and 78% in each respective arm. The 60-month OS rates were 93% and 86.9%, respectively; data showed a strong positive trend toward longer OS with Darzalex Faspro.

Investigators noted no new safety signals among those who received Darzalex Faspro. In the Darzalex Faspro and monitoring arms, 96.9% versus 82.7% had side effects of any grade, 40.4% versus 30.1% had grade 3 or higher side effects, 29% versus 19.4% had serious side effects, and 1% versus 2% had grade 5 side effects. The most common grade 3 or higher side effect in each arm was hypertension (5.7% versus 4.6%), and the incidence of second primary malignancies was comparable between arms (9.3% versus 10.2%).

Health-related quality of life outcomes with Darzalex Faspro appeared to be consistent across multiple measures and domains. Similar mean changes between baseline and week 112 occurred in both treatment arms.

The European Commission approved subcutaneous Darzalex Faspro for this smoldering multiple myeloma population in July 2025 based on findings from the AQUILA trial. Additionally, the FDA’s Oncologic Advisory Drug Committee voted in favor of Darzalex Faspro’s benefit/risk profile for those with high-risk smoldering multiple myeloma in May 2025. 

“Phase 3 AQUILA study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma,” by Dr. Meletios Athanasios Dimopoulos. Presented at the 2025 Society of Hematologic Oncology Annual Meeting (SOHO); Sept. 3-6, 2025; Houston, TX. MM-691.

“European Commission approves DARZALEX (daratumumab) as the first licensed treatment for patients with high-risk smouldering multiple myeloma,” by Johnson & Johnson. News release; July 23, 2025.

“May 20-21, 2025 Meeting of the Oncologic Drugs Advisory Committee (ODAC) - Day 1. Streamed live May 20, 2025,” by U.S. Food and Drug Administration. https://www.youtube.com/live/iSGFdhMgh1E

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Articles

Subcutaneous Darzalex Faspro (daratumumab and hyaluronidase-fihj) significantly reduced the risk of disease progression or death in high-risk smoldering multiple myeloma patients compared to active monitoring. The phase 3 AQUILA study demonstrated a 51% reduction in progression risk, with a median progression-free survival not reached in the treatment arm. Darzalex Faspro showed a favorable safety profile and maintained patients' quality of life. The European Commission approved its use in July 2025, and the FDA's advisory committee endorsed its benefit/risk profile for high-risk patients.

Data from the AQUILA study support the use of fixed-duration subcutaneous Darzalex Faspro as an early treatment option in high-risk smoldering myeloma. 

Subcutaneous Darzalex Faspro Extends PFS in Smoldering Myeloma 

Results from the phase 3 VERONA trial were presented at the 2025 Society of Hematologic Oncology Annual Meeting.

Patients with revised international prognostic scoring system intermediate and high-risk myelodysplastic syndrome (MDS) did not experience an overall survival (OS) improvement from the treatment combination of Venclexta (venetoclax) plus azacitidine when compared with placebo, study results have shown.

In the combination arm, the median OS was 22.18 months versus 21.68 months in the placebo arm. The modified overall response rate (ORR) in the Venclexta/azacitidine arm was 76.2%. The marrow complete response (CR) rate was 57.8%, the partial response (PR) rate was 0.4% and the CR rate was 18%. In the placebo arm, the modified ORR was 57.7%, the marrow CR rate was 37.5% and the CR rate was 20.2%.

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

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

Neutropenia: low count of neutrophils, a type of white blood cell.

Anemia: low count of healthy red blood cells.

Thrombocytopenia: low count of platelets.

The overall hematological improvement in the combination arm was 49.4% compared with 41.2% in the placebo arm. The transfusion independence rates were 55.7% versus 33.6%, respectively. The median duration of transfusion independence was 183 days vs 294 days.

“Subgroup analyses [showed] [Venclexta] plus azacitidine trended toward an mOR benefit versus placebo plus azacitidine for patients with more than 5% to less than 20% bone marrow blasts for ASXL1, TP53 and RUNX1 mutations at baseline,” Dr. Guillermo Garcia-Manero, chair ad interim in the Department of Leukemia, Division of Cancer Medicine, fellowship program director in the Department of Leukemia, and Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research among other titles, at The University of Texas MD Anderson Cancer Center in Houston, said during the presentation.

A total of 509 patients were randomly evenly assigned to either the combination or placebo arms. Patients were given Venclexta at 400 mg by mouth daily on days 1 to 14 plus azacitidine at 75 mg/m

 intravenously or subcutaneously for seven of the first nine days. The placebo plus azacitidine arm matched the combination arm’s dosing. Patients continued treatment until relapse, progressive disease, hematopoietic stem cell transplant (HSCT) or unacceptable toxicity. Patients then transitioned to follow-up.

The median follow-up was 41.2 months, the median duration of treatment was 6.4 months and the median number of cycles was six.

No new safety signals were observed. The most common any-grade treatment-emergent side effects included neutropenia (77.3% versus 60.2%), thrombocytopenia (66.3% versus 58.9%), anemia (44.7% versus 38.2%) and constipation (42.4% versus 50.4%) between the combination and placebo arms of the trial, respectively.

Serious side effects leading to treatment discontinuation occurred in 41.6% of patients in the combination arm and 55.3% of patients in the placebo arm, while dose interruption was noted in 78.8% versus 67.9% of patients and dose reduction of Venclexta or placebo was found in in 12.5% versus 6.9% while azacitidine was 48.6% versus 27.2%.

Side effects leading to death included disease progression (1.6% versus 0.8%), septic shock (1.2% versus 0.8%), sepsis (0.4% versus 0.8%) and acute myeloid leukemia transformation (0.4% versus 0.8%) among patients in the combination and placebo arms, respectively. The most common cause of death was disease progression (39.2% versus 40.7%) and side effects (10.6% versus 11.4%).

Garcia-Manero G, Platzbecker U, Fenaux P, et al. Primary analysis of the randomized phase 3 VERONA study of venetoclax plus azacitidine versus placebo with azacitidine in patients with treatment-naïve, intermediate and higher-risk myelodysplastic syndromes. Presented at the 2025 Society of Hematologic Oncology Annual Meeting, Houston, TX; September 3-6, 2025. Abstract MDS-1497.

The phase 3 VERONA trial evaluated the efficacy of Venclexta (venetoclax) plus azacitidine in patients with intermediate and high-risk myelodysplastic syndrome (MDS). Results indicated no significant improvement in overall survival compared to placebo. The combination arm showed a higher modified overall response rate and marrow complete response rate. Subgroup analyses suggested potential benefits for specific genetic mutations. Common side effects included neutropenia and thrombocytopenia, with serious side effects leading to treatment discontinuation in a notable percentage of patients. The trial highlighted the need for further research to optimize treatment strategies for MDS.

Results from the phase 3 VERONA trial were presented at the 2025 Society of Hematologic Oncology Annual Meeting.

Venclexta And Azacitidine Fail to Improve MDS Survival

Adding Zyprexa to ondansetron cut nausea and vomiting safely in abdominal/pelvic radiation with low-emetogenic capecitabine.

Among patients receiving abdominal/pelvic radiotherapy or concurrent chemoradiation with low-emetogenic oral capecitabine, the addition of Zyprexa (olanzapine) to standard antiemetics may safely and effectively prevent radiation-induced nausea and vomiting (RINV), according to data from a phase 3 placebo-controlled trial presented at 

Safety data from the trial revealed that among patients assigned to receive 5 mg of Zyprexa (148 patients) versus placebo (153 patients), nausea occurred in 14.2% and 83.6%, respectively. Additionally, the incidence of grade 2 (moderate) or greater nausea was 67.3% versus 7.4% with placebo versus olanzapine.

Additionally, vomiting was also reduced with olanzapine; 25.5% of the placebo group and 4.1% of the experimental group experienced any-grade vomiting. Furthermore, the incidence of grade 2 or higher vomiting was 7.8% versus 1.3% in each respective arm. Further data showed that the addition of Zyprexa also reduced the total number of vomiting episodes among patients receiving radiotherapy, with 16.3% of the standard group experiencing 1 to 15 episodes versus 2% of the experimental group; 9.2% versus 2% of each arm experienced more than 15 episodes.

The incidence of grade 2 or higher nausea was also significantly lower for patients across a variety of cancer types. In patients with endometrial cancer, 85.7% of the placebo group and 2.8% of the experimental group experienced grade 2 or higher nausea. The respective rates for endometrial, stomach/pancreatic, and prostate cancers were 92.9% versus 0%, 100% versus 40%, and 19.1% versus 8.7%.

Radiation-induced nausea and vomiting (RINV): nausea and vomiting caused by radiation therapy, particularly in abdominal or pelvic areas.

Antiemetics: medications used to prevent or treat nausea and vomiting.

Quality of life (QOL): a measure of a patient's overall well-being and ability to perform daily activities.

“The addition of 5 mg Zyprexa to standard ondansetron therapy is found to be safe and effective for preventing nausea and vomiting in patients receiving abdominal/pelvic radiation therapy, and those undergoing concurrent chemoradiation with low-emetogenic oral capecitabine,” Meenu Vijayan, MPharm, assistant professor at the Amrita School of Pharmacy, said in the presentation. “Our study was a single-center study. Future studies involving multiple centers and a large number of patients are recommended to corroborate our findings.”

Patients 18 years or older who were receiving abdominal/pelvic radiotherapy and were previously radiotherapy naïve were randomly assigned to receive 4 milligrams of twice daily ondansetron (Zofran) and either 5 mg of oral daily Zyprexa or matching placebo. The study assessed efficacy and safety using the Common Terminology Criteria for Adverse Events (CTCAE) scale, including a nausea and vomiting diary, as well as anxiety and depression using the Hamilton Rating Scale, and quality of life (QOL) using the EORTC QLQ C30 questionnaire.

Patients in the standard and experimental groups, respectively, had a mean age of 63.82 versus 62.32, 58.2% versus 62.8% were males, and 67.3% versus 70.3% had comorbidities. Furthermore, 18.3% versus 19.6% had a history of smoking, 24.8% versus 23% had a history of alcohol, and 50.3% versus 54.7% had a family history of cancer in respective groups. In total, 56.9% versus 53.4% of each group received concurrent capecitabine and 30.7% versus 31.1% received hormone therapy.

The most common cancer types in the standard and experimental groups included rectal cancer (50.3% versus 48.6%), prostate cancer (30.7% versus 31.1%), and endometrial cancer (9.2% versus 9.5%). The most common type of radiotherapy was image-guided radiation therapy (88.9% versus 83.1%) and the most common radiotherapy site was the pelvic area (91.5% versus 93.2%). Patients in each group received a mean dose of 222.58 Gy/day versus 222.01 Gy/day, with a mean duration of 23.67 days versus 23.76 days.

Additional findings from the trial revealed that treatment with Zyprexa reduced mean anxiety scores versus placebo. A similar trend was observed for mean depression scores. Additionally, mean changes in QOL score in the functional scale from baseline to radiotherapy universally favored the experimental, particularly for emotional functioning. This trend was observed in the symptom scale as well, with significant improvements noted in nausea/vomiting, insomnia, and loss of appetite.

“Phase 3 randomized placebo-controlled trial on repurposing Zyprexa for prevention of radiotherapy-induced nausea and vomiting (RINV)” by Dr. M. Vijayan, et al., 

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The addition of Zyprexa (olanzapine) to standard antiemetic therapy significantly reduces radiation-induced nausea and vomiting (RINV) in patients undergoing abdominal/pelvic radiotherapy or concurrent chemoradiation with capecitabine. A phase 3 trial demonstrated that Zyprexa decreased the incidence and severity of nausea and vomiting compared to placebo. The study also showed improvements in anxiety, depression, and quality of life metrics. While the trial was single-center, further multi-center studies are recommended to validate these findings and potentially establish Zyprexa as a standard adjunctive treatment for RINV.

Zyprexa Added to Standard Antiemetics Reduces Nausea, Vomiting in Radiation

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), Columvi (glofitamab) plus chemotherapy with gemcitabine and oxaliplatin (GemOx) demonstrated enhanced survival outcomes compared with Rituxan (rituximab) plus GemOx, according to a two-year follow-up data from the phase 3 STARGLO trial presented at the 

Efficacy data from the trial revealed that after a median follow-up of 24.7 months, Columvi plus GemOx exhibited superior overall survival versus Rituxan/GemOx; the median overall survival was not evaluable versus 13.5 months. Additionally, the 24-month overall survival rate in each arm was 54.4% versus 33.6%. The median progression-free survival in each arm was 13.8 months versus 3.6 months, with respective 18-month progression-free survival rates of 46.5% versus 23.0%.

The objective response rates in the Columvi and Rituxan arms were 68.3% versus 40.7%. Furthermore, the complete response rate with Columvi was 58.5% versus 25.3% with Rituxan. Among responders to Columvi, the median duration of complete response was not reached versus 24.2 months for responders to Rituxan. A total of 42.1% of the Columvi arm and 17.6% of the Rituxan arm had an ongoing complete response at data cut-off.

Following the end of treatment, the median overall survival and progression-free survival was not estimable in the Columvi arm. The respective 12-month overall survival and progression-free survival rates were 89.3% and 82.4%.

“With 2-year follow-up data of the [phase 3] STARGLO trial, Columvi/GemOx continues to show a sustained benefit in overall survival, progression-free survival, and response compared to [Rituxan]/GemOx,” Dr. Jeremy S. Abramson, director of the Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital and a professor of Medicine at Harvard Medical School, said in the presentation. “We saw that more than half of patients remain alive after Columvi/GemOx, and the majority of responders were not only alive, but progression-free.”

Patients in the phase 3 trial were randomly assigned to receive Columvi plus GemOx (183 patients) or Rituxan plus GemOx (91 patients). Those in the Columvi arm received step-up dosing in cycle one, then a 30 milligram (mg) target dose every 31 days starting cycle two, day one. Patients were given eight cycles of Columvi with GemOx followed by four cycles of Columvi as monotherapy.

In the Rituxan and Columvi arms, respectively, the median age was 69.0 years (range, 20-84) versus 68.0 years (range, 22-88), 58.2% versus 57.4% of patients were male, and 56.0% versus 47.0% were Asian. A total of 62.6% versus 62.8% had one prior line of therapy, 51.6% versus 57.9% were primary refractory to last treatment, and 90.9% versus 88.9% had an ECOG performance status of zero or one. Furthermore, 77.8% versus 66.7% had Ann Arbor stage 3 or 4 disease, 15.6% versus 12.6% had bulky disease of 10 centimeter or greater, and 8.8% versus 7.7% received prior CAR-T cell therapy.

The primary end point of the trial was overall survival. Secondary end points included independent review committee–assessed progression-free survival and complete response rates, with a landmark analysis of patients with complete responses at end of treatment performed.

Among those treated with Rituxan and Columvi, 17.0% versus 52.3% experienced serious side effects. Furthermore, 40.9% versus 76.7% experienced grade 3 (serious) or higher side effects, including 4.5% versus 7.0% of patients on each respective arm dying. Side effects leading to treatment discontinuation occurred in 12.5% and 25.6% of the Rituxan and Columvi arms.

In the Columvi arm, the incidence of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was 44.8% and 2.3%, with respective grade 3/4 rates of 2.3% and 0.6%. Infections of any grade occurred in 29.5% and 55.2% of the Rituxan and Columvi arms, respectively, with 9.1% and 16.9% of patients experiencing grade 3 (serious)/4 (life-threatening) infections, and 3.4% versus 3.5% dying from infections.

"Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO" by Dr. Jeremy S. Abramson, et al. American Society of Clinical Oncology Annual Meeting.

Columvi plus chemo had enhanced survival outcomes vs Rituxan plus chemo in patients with relapsed/refractory diffuse large B-cell lymphoma. 

Roman Fabbricatore

Subcutaneous Darzalex Faspro Extends PFS in Smoldering Myeloma

Venclexta And Azacitidine Fail to Improve MDS Survival

Zyprexa Added to Standard Antiemetics Reduces Nausea, Vomiting in Radiation

Columvi Combo Enhances Survival Outcomes in R/R Lymphoma Subgroup

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