Morgan Bayer

More than half of patients responded to treatment with Jakafi (ruxolitinib) plus Rezurock (belumosudil) to treat graft-versus-host disease (GVHD), according to data from a small study presented at the 2024 Tandem Meetings on Transplantation & Cellular Therapy.

“Response was observed with the combination despite progression on both agents as monotherapy, which may suggest synergistic effects in targeting different inflammatory pathways. The combination is tolerable, delays the need for alternative therapies, and facilitates the tapering of corticosteroids,” investigators wrote in the poster.

Among 20 patients observed in the study, the 55% overall response rate (ORR; percentage of patients who had a complete or partial response to treatment), included one (5%) complete response (CR; resolution of GVHD) and seven (35%) partial responses (PR) in patients at any time during the analysis.

Combination therapy with Jakafi and Rezurock showed promise in treating graft-versus-host disease, according to a small study.

Patients who did not respond to either Jakafi or Rezurock alone showed improved outcomes with the combination therapy, including complete or partial responses.

The majority of patients experienced a reduction in the need for other immunosuppressive agents after starting the combination therapy.

Side effects were generally manageable, although some patients developed pneumonia and upper respiratory infections.

Further large-scale studies are needed to fully assess the effectiveness, safety and long-term benefits of this combination therapy for GVHD.

However, one patient was excluded due to insufficient treatment time. There were three patients (15%) who experienced PR and then progression, six patients who had no response (30%), two patients who progressed (10%) and one patient who experienced a mixed response (5%).

The median time to response was 91 days, the duration of response was 48 days, and the median time to progression after a response was 28 days. Among the three patients who did not respond to Jakafi or Rezurock monotherapy, the combination therapy led to one patient showing a CR and two patients showing a PR.

There were five patients (25%) who discontinued treatment after a median of 125 days and all other immunosuppressive agents (drugs that impede the immune system to stop GVHD) were either decreased or discontinued in all patients that had a response to the combination.

According to response by organ system, there were seven organ types addressed: upper gastrointestinal (10% of patients had CR), liver (15% of patients had CR), lung (5% had CR, 15% each had either PR or progression), musculoskeletal (5% each had either PR or progression), ocular (5% each had either CR, PR, or progression), oral (10% each had either CR or progression and 15% had PR) and skin (5% each had either CR or PR).

Patients included in the analysis had previously undergone allogeneic hematopoietic cell transplantation, developed GVHD, and received the Jakafi and Rezurock combination between Feb. 1, 2022, and Aug. 30, 2023. Eligible patients could have any disease or transplant type and the effects of the combination therapy were monitored for up to 12 months from initiation.

The majority of patients were female (60%) with either myeloablative (65%) or reduced intensity (35%) conditioning regimens. Patients received either tacrolimus (Prograf) and methotrexate (MTX) (90%) or tacrolimus, MTX, and anti-thymocyte globulin (10%). The graft source received was either peripheral blood (95%) or bone marrow (5%) and the donor type was either matched but unrelated (75%) or related to the patient (25%).

The overall chronic GVHD (cGVHD) grade at diagnosis was either mild (45%), moderate (40%), or severe (15%), and the cGVHD at the onset of the combination was also mild (10%), moderate (25%), or severe (65%). For the best response cGVHD grade 10% of patients had mild best response, 30% had moderate, 55% had severe and 5% had CR.

Regarding side effects, there were no patients who had or developed cytomegalovirus (a common type of virus known as CMV), Epstein-Barr virus, graft failure or relapse disease, and there was no worsening of cytopenia.

However, four patients (20%) developed pneumonia and two developed (10%) an upper respiratory infection. Rezurock was decreased in one patient because of side effects not mentioned in the poster but then tolerated at the decreased dose, and one patient died while receiving the combination therapy.

Historically, Jakafi and Rezurock monotherapy has an ORR of 76%and 65%, respectively, according to prior studies published in 

. Other commonly used treatments have a lower response rate of 26%, as shown in the REACH3 study. Both Jakafi and Rezurock are well-tolerated medications with different primary targets: Jakafi targets the JAK/Stat pathway, whereas Rezurock targets ROCK2.

“Possible synergistic effects of combination therapy, targeting GVHD from multiple inflammatory pathways may yield higher response rates [and] possible underlying changes in the pathophysiology and manifestations of chronic GVHD over time, [which] could support re-introducing previously failed therapies for use in combination with other agents,” investigators hypothesized.

Moving forward, “large-scale studies [are] warranted to evaluate the efficacy, safety, and durability of response to combination therapy, though there may be overlapping downstream effects of STAT3 and STAT5,” they noted.

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Jakafi plus Rezurock showed promise in treating graft-versus-host disease in patients who underwent undergone allogeneic hematopoietic cell transplantation. 

Drug Duo Is Efficacious in Treating Posttransplant GVHD 

Nearly all patients responded to the CAR-T cell therapy, Carvykti (ciltacabtagene autoleucel; cilta-cel), in a recent trial evaluating the agent in patients with relapsed or refractory multiple myeloma.

These findings were presented by Dr. Jens Hillengass, at the 2024 Tandem Meetings on Transplantation & Cellular Therapy.

Patients included in the phase 2, multicohort CARTITUDE-2 trial were separated into two groups: those who received one to three prior lines of therapy (cohort A; 20 patients) and those with relapse after first-line treatment (cohort B; 20 patients). As of April 2023, both cohorts had durable results at the median follow-up (cohort A, 29.9 months; range, 3.3 to 35.6; cohort B, 27.9 months; range, 5.2 to 32.1).

Carvykti, a CAR-T cell therapy, demonstrated high response rates in patients with relapsed or refractory multiple myeloma.

Both cohorts in the CARTITUDE-2 trial showed durable responses with high rates of MRD negativity, indicating a lack of detectable cancer DNA in blood samples.

Patients experienced rapid responses to treatment, with median times to first and best response reported.

Safety data indicated manageable side effects, with most patients experiencing cytopenia-related effects, and one neurotoxicity event reported in cohort B.

MRD negativity, which is a lack of detectable cancer DNA in blood samples, occurred in 100% of MRD-evaluable patients (17 patients) in cohort A and 93.3% of MRD-evaluable patients (15 patients) in cohort B. Of the patients evaluable for sustained MRD negativity at six months or more (cohort A, 11 patients; cohort B, 13 patients), eight (72.7%) and 10 (76.9%), respectively, experienced sustained MRD negativity, while among those at 12 months or more (cohort A, 14 patients; cohort B, 13 patients) seven (50.0%) and eight (61.5%) experienced the same outcome.

“…And not all patients were evaluable for MRD and that can sometimes be challenging,” Hillengass professor of oncology and internal medicine, chief of myeloma, vice chair for research in the Department of Medicine at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, noted.

The objective response rate (ORR; percentage of patients whose disease shrinks or disappears from treatment) in cohort A was 95%, including a stringent complete response (sCR; no detectable plasma cells in the bone marrow) rate of 85%, a CR (no disease detectable) rate of 5%, and very good partial response rate (VGPR) rate of 5%, and was 100% in cohort B, including an sCR rate of 73.7%, CR rate of 15.8% and VGPR rate of 10.5%.

In cohort A, median time to first response was 0.99 months (range, 0.7 to 3.3) and median time to best response was 3.25 months (range, 0.9 to 13.6), with a 24-month duration of response (DOR) rate of 73.3% , while cohort B demonstrated median times of 0.95 months (range, 0.9 to 9.7) and 5.1 months (range, 0.9 to 11.8), with a 24-month DOR rate of 70.5%.

At that time of the median follow-up the overall survival (OS; time patients live before death of any cause), progression-free survival (PFS; time patients live before their disease worsening), and duration of response (DOR) were not estimable in both cohorts. However, the 24-month OS rates in cohorts A and B were 75% and 84.2%, respectively, and the 24-month PFS rates were 75% and 73.3%.

There were no new safety signals reported; however, one neurotoxicity event occurred in cohort B. Regarding grade 3 and 4 (moderate to severe) side effects of special interest, two patients (10%) in cohort A and 1 patient (5.3%) in cohort B experienced cytokine release syndrome (CRS; when the body releases too many inflammatory molecules, called cytokines, into the blood). The median time to onset of CRS was seven days in cohort A and eight days in cohort B, and the median duration was three and four days, respectively.

Other grade 3 and 4 treatment-emergent side effects in cohorts A and B included CAR T-cell neurotoxicity (5% and 5.3%, respectively) and other neurotoxicity (5% and 5.3%). Movement and neurocognitive were found only in cohort B (5.3%), and second primary malignancy was also found only in cohort B (5.3%).

Overall, cytopenia-related grade 3 and 4 side effects in cohorts A and B were neutropenia (95% and 89.5%, respectively), lymphopenia (80% and 47.4%), thrombocytopenia (40% and 26.3%), anemia (45% and 47.4%) and leukopenia (60% and 31.6%).

Patients in cohort A had 1 to 3 prior lines of therapy and were lenalidomide (Revlimid) refractory MM, while patients in cohort B had experienced early relapse of less than 12 months after autologous stem cell transplant (ASCT) or the start of antimyeloma treatment if no transplant was conducted.Specifically in cohort B, 16% of patients had high-risk cytogenetic abnormalities, 79% were refractory to their last lines of therapy, 16% had triple-class refractory disease and 79% had prior ASCT.

The median age was 60 years in cohort A and 58 years in cohort B, and the majority of patients were male in both cohorts (65% and 73.7%, respectively). Regarding race, 90% were White and 10% were Black in cohort A, compared with 73.7% and 10.5%, respectively cohort B.

“We believe these [data] show that early introduction of cilta-cel in these patient cohorts is promising, and CARTITUDE-4 trial has also done a phase 3 study evaluating these early lines of therapy,” Hillengass stated.“Cohort A provides insight into longer-term survival outcomes that may be expected in the CARTITUDE-4 trial and cohort B data highlight the durable efficacy of cilta-cel in patients with early relapse where there is unmet need.”


Most patients with relapsed or refractory multiple myeloma responded to treatment with the CAR-T cell therapy, Carvykti, according to a small study. 

Early Intro to Carvykti Is ‘Promising’ for Patients With Myeloma

Knowing the specifics of renal cell carcinoma and the disease’s tumor stages may help care teams determine what may be a patient’s prognosis and risk for recurrence, recent study findings suggest.

, investigators evaluated disease-free survival (the time after treatment when a patient survives without symptoms or signs of cancer) and overall survival rates (the percentage of patients who are still alive after treatment) measured at two and five years.

“Our study provides real-world recurrence and survival rates, (however), a major limitation is the retrospective nature of the analysis,” researchers wrote in the poster.

Understanding the specific details of renal cell carcinoma and its different stages can help healthcare teams predict a patient's prognosis and risk of recurrence.

Real-world data from a recent study presented at a cancer symposium provides insights into disease-free survival and overall survival rates at two and five years for different stages and types of renal cell carcinoma.

The study, although retrospective in nature, used real-world information from a specific institution, offering insights beyond controlled clinical trials.

Patients with clear cell renal cell carcinoma generally showed higher survival rates at two and five years in earlier tumor stages, with rates decreasing as the tumor progressed to stage 3.

The study included patients who underwent routine care and various surgical options for non-metastatic renal cell carcinoma, offering valuable insights for counseling patients about adjuvant therapy in a real-world clinical setting.

Retrospective studies typically compare two groups of patients: those with the disease and a similar group of people without the disease. In this instance, researchers used real-world data, meaning the patients were cared for at a specific institution not necessarily on the basis of a clinical trial, for instance.

The real-world data were organized in three main groups based on stage 1, 2 or 3 of tumor node metastasis and histology: clear cell renal cell carcinoma, papillary renal cell carcinoma and not otherwise specified.

Patients in the clear cell renal cell carcinoma group with tumor node metastasis stage 1 showed two years of disease-free survival of 90.4% and at five years 78.9%. The overall survival for this group was 95.2% at two years and 86.5% at five years. These percentages decrease per tumor node metastasis stage; patients with clear cell renal cell carcinoma tumor node metastasis stage 3 showed a disease-free survival of 70.6% at two years and 46.5% at five years. These patients also had an overall survival of 89.3% at two years and 70% at five years.

For patients in the papillary renal cell carcinoma group with tumor node metastasis stage 1, the disease-free survival was 93.9% at two years and 88.5% at five years. The overall survival was 94.8% at two years and 88% at five years. For patients in this group with tumor node metastasis stage 3, the disease-free survival at two years was 47.1% and 23.6% at five years; the overall survival at two years was 70.4% and 41.1% at five years.

In the not otherwise specified renal cell carcinoma group with tumor node metastasis stage 1, the disease-free survival was 89% at two years and 79.7%. The overall survival was 95.4% at two years and 85.9% at five years. For patients in this group with tumor node metastasis stage 3, the disease-free survival at two years was 73% and 44.6% at five years; the overall survival at two years was 84.5% and 53.5% at five years.

The total disease-free survival at five years for patients with clear cell renal cell carcinoma was 83.2% and the total overall survival was 82.7%. For patients with papillary renal cell carcinoma, the total disease-free survival at five years was 85.9% and the total overall survival was 82%. The total disease-free survival at five years for patients not otherwise specified was 87% and the total overall survival was 77.2%.

The analysis included adults who underwent routine care and either nephron-sparing surgery (a surgical option for patients eligible for preserving renal function) or nephrectomy (removal of part or all of a kidney) for non-metastatic renal cell carcinoma at cancer centers between 2013 and 2022. Patients with clear cell, papillary or not otherwise specified histologies were eligible for inclusion. The primary objective of the review was to assess disease-free survival and overall survival.

Among patients evaluated in the review, 1,291 received nephron-sparing surgery or nephrectomy and 1,271 of these patients (98.5%) had R0 (no microscopic evidence of a remaining tumor) or R1 resection margins (removal of all macroscopic but not microscopic tumors). The median follow-up was 37.8 months. Among all patients included in the review, 754 had clear cell renal cell carcinoma with a mean age of 63.5 years. There were 221 patients who had papillary renal cell carcinoma with a mean age of 62.1 years. There were 165 patients with not otherwise specified renal cell carcinoma and a mean age of 63.3 years. Additionally, 129 patients had other histologies and a mean age of 61 years.

In localized renal cell carcinoma, standard treatments include nephrectomy and risk-adapted adjuvant Keytruda (pembrolizumab). The risk of recurrence is assessed based on findings from clinical trials to guide patient counseling. The real-world data are minimal for recurrence and survival, and real-world outcomes may vary from what is observed in controlled trial settings.

“(Because) our study advises on real-world recurrence and survival rates in patients with different (renal cell carcinoma) types, it may be used to counsel patients with regards to adjuvant therapy in the clinic,” investigators stated in the abstract.

Real-world data demonstrated that knowing a patient’s stage and subtype of renal cell carcinoma, a type of kidney cancer, may provide cancer teams with the information needed to determine potential prognosis and recurrence risk.

Kidney Cancer Subtypes, Tumor Stages May Predict Recurrence, Prognosis

The antitumor activity of immune-stimulating antibody conjugate (ISAC) BDC-1001, when combined with Perjeta (pertuzumab), in various HER2 tumor-expressing cancers, including breast cancer, will be evaluated in a phase 2 trial. This trial includes patients with histologically confirmed HER2-postive breast adenocarcinoma and is designed to observe the antitumor effects of BDC-1001 with or without Perjeta, according to a poster presented at the 

2023 San Antonio Breast Cancer Symposium (SABCS)

“BDC-1001 was well-tolerated in the phase 1 dose-escalation trial that enrolled patients with HER2-expressing solid tumors. Clinical activity observed across different HER2-positive tumor types and in a heterogenous, heavily pretreated patient population: 29% response rate in HER2 evaluable HER2-positive tumors at the recommended phase 2 dose; multiple patients with long-term stable disease,” investigators reported in the poster.

The phase 2 trial is an open-label, multicenter study, and patients with HER2-positive metastatic breast cancer will be randomly assigned into two arms.

The first arm will receive single-agent BDC-1001 intravenously (IV) every two weeks at 20 mg/kg, which was based on safety, clinical efficacy and pharmacokinetics (how the drug moves through and is absorbed in the body) reported from the phase 1 trial.

The second arm will receive the same dose of BDC-1001 every two weeks in combination with an 840 mg/420 mg dose of intravenous Perjeta administered every three weeks.

The primary endpoint of the trial was the objective response rate (patients whose disease responded partially or completely to treatment). Secondary endpoints include evaluating antitumor activity in response to BDC-1001 with or without Perjeta regarding duration of response, disease control rate (patients whose disease shrunk, disappeared or was stable from treatment), progression-free survival (how long a patient lives without their disease spreading or worsening) and overall survival (how long a patient lives following treatment, regardless of disease status) as well as determining safety, tolerability, pharmacokinetics and immunogenicity (the ability for tissues and cells to provoke an immune response.

To be eligible for the phase 2 trial, patients with histologically confirmed HER2-positive breast adenocarcinoma must have been treated previously with Enhertu (trastuzumab deruxtecan) and at least one other prior anti-HER2 therapy.

Prior neoadjuvant (before surgery) or adjuvant (following the main treatment) therapy that resulted in relapse within 12 months of completion of therapy will also be considered as a prior line of treatment.

Patients must have an ECOG performance status of 0 or 1 (patients can perform all of their daily tasks with little to no help) and must agree to biopsy before enrollment in the trial unless the biopsy cannot be accessed safely or clinically feasibly.

Specific exclusions for eligibility are if the patient has a history of treatment with a TLR7, TLR8 or has received a TLR7/8 agonist within 12 months of enrollment. Patients with central nervous system metastases are eligible for the study unless the disease is asymptomatic, clinically stable and hasn’t required steroid treatment for at least 28 days before starting the study treatment.

To assess whether there is a relationship between specific markers found in both the blood and tumor tissue before treatment and how BDC-1001, either alone or combined with Perjeta, works against the tumor, tissue biopsies will be taken at baseline and after treatment.

Pro-inflammatory cytokines and chemokines will also be evaluated as well as examining additional biomarkers in tumor tissue and blood related to tumor and immune biology. This involves analyzing gene expression, mutations, proteins, and tissue images to better understand the biological aspects of the tumor and immune system.

The decision to proceed with the phase 2 trial was based on data received from the phase 1 trial, focusing on dose escalation for patients with HER2 breast cancer. Within phase 1, 131 patients with 16 various unspecified HER2 solid tumor expressions received an increasing 0.5 to 20 mg/kg dose of BDC-1001.

The treatment was tolerated as both a monotherapy and when combined with Opdivo (nivolumab), all patients showed clinical activity across different HER2-positive tumor types in both the heterogenous and heavily treated patient population.

Preclinical research showed that combining a surrogate of BDC-1001 with Perjeta improves the effectiveness against various HER2-expressing tumor models. This formed the basis for considering the combination therapy of BDC-1001 and Perjeta. With the addition of Perjeta, the agent attaches to a different location on the HER2 tumor and boosts the quantity of antibodies attached to the tumor cell surface.

“Enrollment of the phase 2 study is ongoing in the United States, France, Italy and Spain,” investigators stated in the poster.

Research is underway on the immune-stimulating antibody conjugate BDC-1001’s effectiveness against HER2-positive cancers when combined with Perjeta, according to data presented at SABCS.

Morgan Bayer

Drug Duo Is Efficacious in Treating Posttransplant GVHD

Early Intro to Carvykti Is ‘Promising’ for Patients With Myeloma

Kidney Cancer Subtypes, Tumor Stages May Predict Recurrence, Prognosis

Phase 2 Evaluating BDC-1001 Plus Perjeta in HER2-Positive Breast Cancer

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