Carrie L. Kitko, MD is an associate professor of pediatrics, Hematology/Oncology, Ingram Professorship in Pediatric Oncology, in the Department of Pediatrics, and  the medical director of the Pediatric Stem Cell Transplantation Program at Vanderbilt University Medical Center, part of Vanderbilt Children's Hospital. 

Dr Kitko on Clinical Outcomes With Axatilimab According to Prior Lines of Therapy for Chronic GVHD

“We looked at the data in several ways. If [a patient] had been exposed to prior [lines] before receiving axatilimab, response rates still looked excellent, though they were maybe slightly lower [in those exposed to] belumosudil vs ruxolitinib before starting axatilimab. That being said, we’re looking at very small numbers, so it is hard to really make any statistical comparisons of response rates between those 2 drug groups."

Carrie L. Kitko, MD, associate professor, pediatrics, Hematology/Oncology, Ingram Professorship in Pediatric Oncology, Department of Pediatrics, medical director, Pediatric Stem Cell Transplantation Program, Vanderbilt University Medical Center, Vanderbilt Children’s Hospital, discusses the effect of treatment with ruxolitinib (Jakafi) and other immunosuppressive agents on outcomes with the novel colony-stimulating factor 1 (CSF-1R)–blocking antibody axatilimab-csfr (Niktimvo) among patients with chronic graft-vs-host-disease (GVHD).

a post hoc analysis of the phase 1 AGAVE-201 trial (NCT04710576)

2025 Transplantation & Cellular Therapy Meetings

, and showed that treatment with axatilimab produced rapid and durable overall response rates (ORRs) in patients with chronic GVHD, irrespective of the number of previous lines of therapy they received, Kitko reports.

Among all patients treated with axatilimab (n = 241), the ORRs were comparable across subgroups based on prior response, at 64.6% (95% CI, 53.3%-74.9%) for those who previously achieved a complete response (CR) or partial response (PR; n = 82), 62.1% (95% CI, 52.6%-70.9%) for those with no change in response (n = 116), and 62.5% (95% CI, 35.4%-84.8%) for those with disease progression (n = 16). ORRs also appeared to increase slightly with additional prior lines of therapy. For those with exposure to 2 prior lines of therapy (n = 35), the ORR was 51.4% (95% CI, 34.0%-68.6%); for those exposed to 3 prior lines (n = 49), it was 61.2% (95% CI, 46.2%-74.8%); for those exposed to 4 prior lines (n = 49), it was 63.3% (95% CI, 48.3%-76.6%).

For patients who received axatilimab at 0.3 mg/kg, the ORRs were 63.3% (95% CI, 43.9%-80.1%) in the prior CR/PR group (n = 30), 81.3% (95% CI, 63.6%-92.8%) in the no change group (n = 32), and 83.3% (95% CI, 35.9%-99.6%) in the disease progression group (n = 6). The ORRs at this dose were 63.6% (95% CI, 30.8%-89.1%) for those who had received 2 lines of therapy (n = 11), 53.3% (95% CI, 26.6%-78.7%) for those who had received 3 prior lines of therapy (n = 15), and 82.4% (95% CI, 56.6%-96.2%) for those who had received 4 lines of therapy (n = 17).

Patients who received rituximab in the last line of therapy (n = 68) had an ORR of 61.8% (95% CI, 49.2%-73.3%), with a median time to response (TTR) of 1.9 months (range, 0.9-5.8) and a sustained response rate of 43.0% (95% CI, 31%-55%). In those who received belumosudil in the last line of therapy (n = 34), the ORR was 50.0% (95% CI, 32.4%-67.6%), with a median TTR of 1.9 months (range, 0.9-3.9) and a sustained response rate of 26.0% (95% CI, 13%-44%).

These findings suggest that axatilimab may provide a meaningful clinical benefit across different prior treatment histories in chronic GVHD, including in patients previously treated with ruxolitinib or other immunosuppressive agents. However, Kitko cautions against making statistical comparisons between responses obtained according to whether ruxolitinib or belumosudil were previously received due to the small sample size.

Videos

Carrie L. Kitko, MD, discusses outcomes with axatilimab in patients with chronic graft-vs-host-disease according to prior lines of therapy received. 

Dr Kitko on the Utility of Obe-Cel in Pediatric Patients With B-ALL

Carrie L. Kitko, MD, associate professor of pediatrics, Hematology/Oncology, Ingram Professorship in Pediatric Oncology, Department of Pediatrics, medical director, Pediatric Stem Cell Transplantation Program, Vanderbilt University Medical Center, Vanderbilt Children's Hospital, discusses the investigation of obecabtagene autoleucel (obe-cel) for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

Kitko states that she is optimistic about 

increasing pharmaceutical interest in pediatric oncology treatments

, and recent developments in this space. One such advancement is a product called obe-cel, which was developed in the Europe and is now entering global trials, she explains. This product features a slightly different CAR construct than other CD19-targeted CAR T products, binding to CD19 to drive anti-leukemia activity but displaying a lower binding affinity. This lower affinity results in fast on-off kinetics, which is believed to lead to increased T cell persistence and reduced exhaustion, Kitko explains. Moreover, this characteristic may enhance the product's safety profile, she notes.

Several trials have been conducted to evaluate obe-cel's efficacy and safety, Kitko expands, adding that a pediatric-specific trial has shown promising results. The agent was also evaluated in 2 larger studies primarily focused on adults, although some adolescent and young adult patients with either ALL or B-cell lymphomas were included. One of these trials was 

, which demonstrated an overall response rate of 77% with obe-cel in patients with relapsed or refractory B-ALL, Kitko reports. This study also reported a 12-month event-free survival rate of 50%, she emphasizes.

A particularly notable finding from these trials is the low incidence of severe adverse effects. The rate of grade 3 cytokine release syndrome was less than 5%, and instances of neurologic toxicity were rare, Kitko continues. These results suggest that obe-cel could be a safer option compared with existing treatments.

Given these outcomes, Kitko is hopeful that obe-cel could be further developed and expanded into pediatric use in the United States. The potential for obe-cel to provide a safe and effective treatment for pediatric patients is exciting, Kitko says, concluding that she looks forward to the possibility of integrating this innovative therapy into broader clinical practice.

Carrie L. Kitko, MD, discusses the use of obecabtagene autoleucel for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia.

Chronic Graft-Versus-Host Disease (cGVHD) affects 30 to 50% of patients who have received allogeneic hematopoietic cell transplantation (HCT). Many patients with cGVHD fail to respond to available therapies or eventually progress. Sclerosis and lung involvement are often difficult to treat and may lead to poor outcomes.

Blocking CSF-1 / CSF-1R signaling may prevent and treat cGVHD

Axatilimab is an anti-CSF-1R monoclonal antibody targeting macrophage-driven diseases

High-affinity humanized IgG4 monoclonal antibody

Blocks the binding of both CSF-1 & IL-34 ligands

Administered via 30-minute infusion every 2 to 4 weeks

Highly effective in selectively reducing levels of circulating pro-fibrotic/non-classical monocytes

Intermittent dosing allows for monocyte recovery prior to subsequent dose

Phase 1/2 trial enrolled 40 patients; phase 1 dose escalation and phase 2 dose expansion

Study population included patients who were 6 years of age or older with active cGVHD after 2 or more prior treatments and a KPS of 60 or higher

1 patient each in Cohort 1 and 2 (0.15 mg/kg Q2W and 0.5 mg/kg Q2W, respectively)

Primary endpoints: Safety, overall response rate (ORR), recommended phase 2 dose (RP2D)

Primary endpoint: ORR (2014 NIH consensus criteria)

Median age: 59 (16-73); majority were male

65% received myeloablative transplant; 93% received a peripheral blood transplant

65% of patients had at least 4 organs involved

Majority had received at least one of the new FDA-approved therapies

Treatment was well-tolerated with very few discontinuations due to adverse events (AEs)

Most common AEs were increases in AST/ALT, CPK, amylase, and lipase without evidence of end organ damage; periorbital edema

Infection rates were in line with contemporary experience in cGVHD

Best change in normalized Lee Symptom Score (LSS)

Median change (points): -7.8 (range 3.1, -37.6)

16 (53%) of 30 LSS-evaluable patients achieved a 7-point reduction from baseline

Improvement seen regardless of response by NIH consensus criteria

Responses seen in all dose levels and across all organ systems

Axatilimab advances to Pivotal Phase 2 Trial – AGAVE-201

Inclusion: 2 years and older, recurrent or refractory active cGVHD after 2 or more lines of systemic therapy

Stratification factors: Prior therapy (ibrutinib, ruxolitinib, belumosudil)

1:1:1 randomization to 0.3 mg/kg Q2W (N = 70); 1 mg/kg Q2W (N = 70); 3 mg/kg Q4W (N = 70)

Dr Carrie Lynn Kitko discusses updated results from a phase 1/2 study evaluating the safety, tolerability, and efficacy of axatilimab in pts ≥ 6 years of age with active cGVHD despite ≥ 2 prior lines of systemic therapy.

Rapid Readouts: Safety, Tolerability, and Efficacy of Axatilimab, a CSF-1R humanized antibody, for Chronic Graft-versus-Host Disease after 2 or more Lines of Systemic Treatment

Carrie L. Kitko, MD

Articles

Dr Kitko on Clinical Outcomes With Axatilimab According to Prior Lines of Therapy for Chronic GVHD

Dr Kitko on the Utility of Obe-Cel in Pediatric Patients With B-ALL

Rapid Readouts: Safety, Tolerability, and Efficacy of Axatilimab, a CSF-1R humanized antibody, for Chronic Graft-versus-Host Disease after 2 or more Lines of Systemic Treatment