publication date: Dec. 13, 2019

Clinical Roundup

PD-1 inhibitor treatment prior to stem cell transplant is safe, effective in classic Hodgkin lymphoma

A new analysis shows that a donor stem cell transplant following treatment with an immune checkpoint inhibitor is generally safe and produces good outcomes for patients with Hodgkin lymphoma, easing concerns that these patients are at heightened risk for severe immune-related complications.

The study, presented at the 61st American Society of Hematology Annual Meeting by Reid Merryman, attending physician in the Lymphoma Program at Dana-Farber Cancer Institute, also found that post-transplant treatment with the drug cyclophosphamide may lead to improved results for many patients.

The study focused on the safety of donor stem cell transplantation in patients with classic Hodgkin lymphoma who were previously treated with a PD-1 inhibitor, a drug that unleashes an immune system attack on tumor cells. While PD-1 inhibitors produce responses in about 70% of these patients, many develop resistance to the drugs within a few years. For that reason, patients are often recommended for a donor stem cell transplant, which can cure the disease.

Because PD-1 inhibitors let loose an immune system attack, there had been concerns of immune-related problems such as acute graft-versus-host disease, in which immune cells from transplanted tissue attack patients’ normal, healthy tissue. Several previous studies, including one by Dana-Farber investigators, seemed to justify those concerns, but the studies enrolled relatively small numbers of patients and had a short follow-up period.

The new study pooled data from 150 patients at 26 transplant centers across the U.S. and Europe who had undergone a donor cell transplant after a median of 10 doses of a PD-1 or PD-L1 inhibitor. Fifty-nine percent of the patients were treated with cyclophosphamide to lower their risk of GVHD.

At a median of two years after their transplant, 79% of the patients were alive and 65% had no evidence of lymphoma. Twenty-one percent had relapsed. Six months post-transplant, 39% of patients had developed acute GVHD, including 8% who had severe, life-threatening acute GVHD–a rate that was lower than in previous, smaller studies, Merryman noted. Investigators found that patients treated with cyclophosphamide post-transplant generally fared better and had lower rates of chronic GVHD and relapse.

“Our results indicate that treatment with a PD-1 or PD-L1 inhibitor in advance of a donor stem cell transplant is safe and can provide good outcomes for these patients,” said Merryman, “and inclusion of cyclophosphamide treatment as part of GVHD prevention may provide an additional benefit.”


BMS’s liso-cel met primary, secondary endpoints in TRANSCEND NHL 001

Bristol-Myers Squibb Co. said the pivotal study of lisocabtagene maraleucel (liso-cel) an investigational CD19-directed CAR T-cell therapy with a defined composition of purified CD8+ and CD4+ CAR T cells in relapsed/refractory large B-cell lymphomas (TRANSCEND NHL 001) met its primary and secondary endpoints while demonstrating durable responses.

The data were presented during an oral session at the 2019 ASH annual meeting.

“Longer-term follow-up from the TRANSCEND study shows that liso-cel resulted in a rapid, high rate of durable complete responses with low incidence of severe cytokine release syndrome and neurologic events in two and 10 percent, respectively, among patients with relapsed/refractory large B-cell lymphomas,” said Jeremy Abramson, associate professor of medicine at Harvard Medical School and director of the Lymphoma Center at Massachusetts General Hospital. “Additionally, responses with liso-cel were seen across patient groups including high-risk patients such as those with refractory disease, older patients and those with high tumor burden.”

In the study, 344 patients were leukapheresed and 269 patients received liso-cel at one of three dose levels (50 x 106 n=51; 100 x 106 n=177; and 150 x 106 n=41). There were 25 patients that received nonconforming product and there were two instances where product could not be manufactured. Patients were heavily pretreated and had aggressive disease with a median of three prior therapies including 35% with prior autologous or allogeneic hematopoietic stem cell transplant and 67% with chemotherapy-refractory disease. Bridging therapy was administered to 59% of patients.

Among patients evaluable for efficacy (n=256), the overall response rate was 73% (187/256, 95% CI: 67 – 78) with 53% of patients (136/256, 95% CI: 47 – 59) achieving a complete response. Responses were similar across all patient subgroups. The median duration of response for all patients was not reached (95% CI: 8.6 months – NR) at a median follow-up of 12 months (95% CI: 11.2 – 16.7). Median progression-free survival was 6.8 months (95% CI: 3.3 – 14.1) and median overall survival was 21.1 months (95% CI: 13.3 – NR). The median PFS and OS for patients who achieved a CR was not reached with 65.1% of patients progression free and 85.5% of patients alive at 12 months, respectively.

BMS said that based on results from TRANSCEND NHL 001 it expects to complete the submission of a Biologics License Application to FDA by the end of the year.


Phase II KarMMa study of ide-cel in relapsed, refractory multiple myeloma meets ORR primary endpoint

Results from the KarMMa study, a pivotal, open-label, single arm, multicenter, phase II study of idecabtagene vicleucel met its primary endpoint of overall response rate in the treatment of relapsed and refractory multiple myeloma.

The study is sponsored by Bristol-Myers Squibb Co. and bluebird bio Inc.

KarMMa, which evaluated the efficacy and safety of the companies’ lead investigational BCMA-targeted chimeric antigen receptor CAR T-cell therapy candidate for patients with relapsed and refractory multiple myeloma also met a key secondary endpoint, complete response rate.

The primary endpoint overall response rate was 73.4% (n=94/128) across three doses. The response rate was dose-dependent, 50.0% (n=2/4) in the lowest, 68.6% (n=48/70) in the middle and 81.5% (n=44/54) in the highest. The complete response rates were 25%, 28.6% and 35.2%, respectively.

Median duration of response was 10.6 months and median progression-free survival was 8.6 months.

KarMMa enrolled 140 patients, of whom 128 patients were treated with ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells. All treated patients were exposed to at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and all were refractory to their last regimen. Ninety-four percent of patients were refractory to an anti-CD38 antibody and 84% percent were triple refractory (refractory to an IMiD agent, PI and anti-CD38 antibody).

The median follow-up duration for all subjects was 11.3 months.

Overall, the safety results were consistent with those observed in the phase 1 CRB-401 study, which evaluated the preliminary safety and efficacy of ide-cel.

“For multiple myeloma patients who have relapsed and become refractory to current treatment options, there remains a high unmet need, as these patients typically experience low response rates, short response durations and poor survival,” Kristen Hege, senior vice president of Hematology/Oncology and Cell Therapy and Early Clinical Development for Bristol-Myers Squibb, said in a statement.

“The KarMMa study provides further support for ide-cel as a potential therapeutic option in this heavily pre-treated patient population, and we are encouraged by these data, especially the outcomes observed at the highest target dose of 450 x 106 CAR+ T cells,” Hege said.

“We are actively preparing for submission of these data to health authorities for proposed initial registration of ide-cel as a first-in-class BCMA-targeted CAR T-cell therapy.”


Seattle Genetics announces positive OS, PFS, ORR for tucatinib in HER2+ breast cancer

Seattle Genetics Inc. announced positive pivotal data from the HER2CLIMB trial evaluating tucatinib in patients with HER2-positive metastatic breast cancer.

“Tucatinib demonstrated a statistically significant and clinically meaningful benefit in overall survival, progression-free survival and objective response rate compared to the control arm,” said Roger Dansey, chief medical officer at Seattle Genetics. “We plan to submit a New Drug Application to FDA and a Marketing Authorization Application to the European Medicines Agency by the first quarter of 2020, with the goal of bringing a much-needed new medicine to patients.”

The results were presented at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. The data presented include the primary endpoint of PFS as assessed by blinded independent central review in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including OS as well as PFS in patients with brain metastases at baseline.

The HER2CLIMB trial compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine. Patients had received a median of four prior lines of therapy overall and three lines in the metastatic setting.

Forty-seven percent of the patients enrolled in the trial had brain metastases at the time

of enrollment. HER2CLIMB is the first randomized pivotal trial completed to enroll patients with metastatic HER2-positive breast cancer who have untreated or previously treated and progressing brain metastases.

Tucatinib is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2.

“Following progression on trastuzumab, pertuzumab and T-DM1 in the metastatic HER2-positive breast cancer setting, there is no single standard of care regimen and clinical trial participation is often strongly encouraged. There is a significant unmet medical need for these patients, particularly those who develop brain metastases,” said Rashmi Murthy, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center.

“The addition of tucatinib to the commonly used combination of trastuzumab and capecitabine improved overall survival, reducing the risk of death by 34 percent compared to trastuzumab and capecitabine alone. The results from HER2CLIMB demonstrate tucatinib has the potential to become a new treatment option for patients who have been previously treated with multiple anti-HER2 agents, including patients with and without brain metastases.”


ctDNA may help predict recurrence in patient with early triple-negative breast cancer

The presence of circulating tumor DNA in early-stage triple-negative breast cancer helped predict the risk of recurrence in women who had undergone surgery after neoadjuvant chemotherapy, a study found.

The results of the study—funded by the Vera Bradley Foundation for Breast Cancer and the Indiana University Grand Challenge Precision Health Initiative—were presented at the 2019 San Antonio Breast Cancer Symposium. The trial was managed by the Hoosier Cancer Research Network and enrolled at 26 sites across the U.S.

In this study, the authors and colleagues analyzed plasma samples that had been collected from patients enrolled in the BRE12-158 clinical trial, which studied genomically directed therapy versus physician’s choice of treatment after preoperative chemotherapy in patients with triple-negative breast cancer. The trial enrolled 196 women, and ctDNA was sequenced in 142 patients using the FoundationOne Liquid Test.

Mutated ctDNA was detected in 90 of the patients, representing 63 percent. TP53 was the most commonly mutated gene, followed by others that are commonly associated with breast cancer.

At 17.2 months of follow-up, detection of ctDNA was significantly associated with inferior distant disease-free survival. Patients with ctDNA had a median DDFS of 32.5 months, while the patients without ctDNA had not reached the median.

At 24 months, the DDFS probability was 56 percent in ctDNA-positive patients, compared with 81 percent in ctDNA-negative patients. In multivariate analysis, when the researchers controlled for factors including residual cancer burden; tumor size, grade, and stage; age; and race, detection of ctDNA remained independently associated with inferior DDFS. Overall, ctDNA-positive patients were three times as likely to have distant disease recurrence than ctDNA-negative patients.

Detection of ctDNA was also associated with inferior overall survival; ctDNA-positive patients had 4.1 times increased risk of death compared with ctDNA-negative patients.

“This study establishes that triple-negative breast cancer patients who have ctDNA after neoadjuvant therapy have a higher risk of recurrence,” Schneider said. “This may set the stage for further clinical trials for these high-risk patients, evaluating novel ways to prevent recurrence.”

The authors said a clinical trial expected to begin in 2020 will further examine ctDNA’s potential in guiding therapy for those patients who are at high risk of recurrence. They also noted that sequencing technology is developing rapidly, and will likely become more sensitive and more specific over time.

“For patients who have triple-negative breast cancer with residual disease, the risk of recurrence is exceptionally high,” said the study’s senior author, Bryan P. Schneider, professor of medicine and medical and molecular genetics at Indiana University School of Medicine. “Novel therapies and technologies are critical, including those that can potentially predict the risk of relapse.”

ctDNA, or tumor DNA derived from plasma, is being explored as a way to detect cancer, guide treatment, and monitor patients during remission. The presence of ctDNA can signal the presence of cancer.

Conversely, the authors—researchers in the Indiana University Melvin and Bren Simon Cancer Center and the Vera Bradley Foundation Center for Breast Cancer Research—said that superior outcomes for those who did not have ctDNA could potentially set the stage for clinical studies evaluating the ability to reduce post-surgical treatment for these patients.

The diagnostic used in the study was Foundation Medicine’s FoundationOne Liquid Test.


Extended follow-up phase III data underscore sustained efficacy and safety of Imbruvica in CLL

The phase III E1912 clinical study showed superior progression-free survival and overall survival in patients with chronic lymphocytic leukemia new to treatment.

AbbVie sponsors the study, which was designed and conducted by the ECOG-ACRIN Cancer Research Group and sponsored by NCI.

These results demonstrated the benefits of Imbruvica (ibrutinib) plus rituximab compared to a standard chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab for previously untreated patients with CLL aged 70 years or younger, the company said.

These results were presented Dec. 7 at the American Society of Hematology annual meeting, and served as the basis of the recent supplemental New Drug Application FDA, to expand the Imbruvica prescribing label in CLL.

Additionally, a new integrated analysis of up to six years of long-term follow-up from the phase III RESONATE and RESONATE-2 studies will be presented on Dec. 8 at ASH, evaluating the use of Imbruvica monotherapy in previously untreated patients. Results showed better PFS, OS and overall response rate, with good tolerability compared to use in the relapsed/refractory setting.

“These latest findings add to the extensive clinical evidence supporting the use of Imbruvica, the most comprehensively studied BTK inhibitor in CLL, as both a single-agent and as a combination regimen to improve patient outcomes in early lines of treatment, which has previously been reserved for chemoimmunotherapy,” Danelle James, Imbruvica Clinical Development Lead of Pharmacyclics LLC, an AbbVie company, said in a statement.

“Phase III RESONATE and RESONATE-2 trials have proven to be cornerstone studies that have significantly advanced the treatment of CLL among a variety of patients—and the latest data presented at this year’s ASH Annual Meeting demonstrate using IMBRUVICA alone and earlier in CLL treatment results in improved patient outcomes,” Paul M. Barr, study investigator of the Phase III RESONATE and RESONATE-2 trials, and associate professor of medicine, Hematology/Oncology at the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, said in a statement. “These results reaffirm the sustained disease control and safety profile of Imbruvica and further support its use as a chemotherapy-free option for previously untreated patients living with this common form of adult leukemia.”

Imbruvica is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.


Phase III TOURMALINE-AL1 trial of Ninlaro in patients with amyloidosis didn’t meet one of two primary endpoints

TOURMALINE-AL1 trial, a phase III, randomized clinical trial evaluating the effect of Ninlaro (ixazomib) in combination with dexamethasone, did not meet the first of the two primary endpoints of significant improvement in overall hematologic response in patients with relapsed or refractory systemic light-chain amyloidosis.

The study is sponsored by Takeda Pharmaceutical Co. The results were presented during an oral session at the 61st American Society of Hematology annual meeting.

Hematologic responses were seen in 53% versus 51% of patients receiving Ninlaro plus dexamethasone versus physician’s choice (odds ratio 1.10 [95% CI 0.60-2.01], p=0.762) as assessed by an adjudication committee. The second primary endpoint of two-year vital organ deterioration or death was not mature at the time of analysis. Other endpoints studied including vital organ progression free survival, hematologic PFS, time to treatment failure and time to subsequent therapy were numerically higher in the Ninlaro plus dexamethasone arm compared to the physician’s choice arm.

Takeda said the company is committed to making data available to researchers to continue investigation of this disease. Ninlaro is not approved as a treatment for AL amyloidosis.

“AL amyloidosis is a rare condition, for which prognosis and patient outcomes are poor. Current treatments are often retrofitted from therapies used for multiple myeloma,” said Angela Dispenzieri, Mayo Clinic, and the trial’s principal investigator and lead author. “For a phase III study that did not meet its primary endpoint, this trial provides interesting information for this community and for future studies. Ongoing research and development to investigate potential treatment options for this underserved patient population is critical.”


Phase III SOPHIA study shows margetuximab didn’t reach significance for OS in HER2+ metastatic breast cancer

MacroGenics Inc. has presented updated results from the phase III SOPHIA study comparing margetuximab plus chemotherapy versus trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have previously been treated with anti-HER2-targeted therapies.

Margetuximab is an investigational, immune-enhancing monoclonal antibody derived from the company’s proprietary Fc-engineering technology platform. The data were presented during an oral session at the San Antonio Breast Cancer Symposium by Hope Rugo, director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

Overall survival results favored margetuximab plus chemotherapy compared with trastuzumab and chemotherapy in the intention-to-treat population; however, these data did not reach statistical significance at this second interim analysis as of a September 2019 cut-off after 270 events (median OS=21.6 months versus 19.8 months; hazard ratio [HR]=0.89; 95% CI: 0.69-1.13; P=0.326).

The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in the second half of 2020. A pre-specified exploratory objective of the study was to evaluate the effect of CD16A (Fcγ receptor) allelic variation on margetuximab activity.

Among the genetically defined subpopulation of patients carrying a CD16A 158F allele, who represent approximately 85% of the human (and SOPHIA study) population, the median OS at the second interim analysis was prolonged by 4.3 months in the margetuximab arm compared to the trastuzumab arm (23.7 months versus 19.4 months; HR=0.79; 95% CI: 0.61-1.04; nominal P=0.087). Among the approximately 15% of patients who were homozygous for the CD16A 158V allele, the trastuzumab arm performed better than the margetuximab arm.

“Patients with later stage HER2-positive metastatic breast cancer need access to new therapies. The updated SOPHIA study results presented today at the second interim survival analysis showed a trend in overall survival favoring margetuximab and are encouraging. Furthermore, margetuximab is the only HER2-targeted agent to show PFS superiority versus trastuzumab in a head-to-head Phase 3 clinical trial,” Rugo said. “The SOPHIA study also includes a pre-specified analysis of CD16A genotype as a predictor of anti-HER2 antibody efficacy, which although exploratory, is the first such prospective clinical analysis and suggests differential benefit in this population.”

As previously reported, margetuximab plus chemotherapy showed a statistically significant improvement in independently-assessed progression-free survival compared to trastuzumab plus chemotherapy in this study as of an October 2018 cut-off after 256 events (median PFS=5.8 months versus 4.9 months; HR=0.76; 95% CI: 0.59-0.98; P=0.033).

An updated investigator-assessed analysis as of a September 2019 cut-off showed consistent results after 430 PFS events (median PFS=5.7 months in the margetuximab arm versus 4.4 in the trastuzumab arm; HR=0.71; nominal P=0.0006). Similarly, at the time of this updated analysis, additional patients were evaluable for response in the ITT population.

Investigator-assessed objective response rate was 25.2% (95% CI: 20.1-30.9%) in the margetuximab arm compared to 13.7% (95% CI: 9.8–18.4%) in the trastuzumab (nominal P=0.0006). The clinical benefit rate (CBR, which includes CR+PR+SD>6 months, was 48.1% (95% CI: 42.0-54.3%) in the margetuximab arm versus 35.6% (95% CI: 29.9-41.6%) in the trastuzumab arm (nominal P=0.0025).

Margetuximab plus chemotherapy has shown a safety profile generally comparable to that of trastuzumab plus chemotherapy in this study. As of the April 2019 cut-off for safety, Grade 3 or greater adverse events occurred in 142 (54%) patients on the margetuximab arm compared to 140 (53%) patients on the trastuzumab arm. Serious adverse events occurred in 43 (16%) patients on the margetuximab arm compared to 49 (18%) patients on the trastuzumab arm.

Infusion-related reactions were more common with margetuximab treatment than with trastuzumab (13% versus 3%) and were mostly Grade 1 or 2 and associated with the first dose. A substudy evaluating shorter, 30-minute infusions of margetuximab in Cycle 2 and beyond showed no effect on safety outcomes, as well as risk or severity of IRR.


Keytruda improved OS in frontline metastatic NSCLC regardless of KRAS status

Keytruda (pembrolizumab) showed improvements in overall survival, progression-free survival and objective response rate as monotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥1%), regardless of KRAS mutational status.

These findings, which are based on an exploratory analysis of the pivotal phase III KEYNOTE-042 trial, were presented in a proffered paper presentation (Abstract #LBA4) at the European Society for Medical Oncology Immuno-Oncology Congress 2019 in Geneva.

“KRAS mutations occur in approximately 20% of people with non-small cell lung cancer, and some previous studies have suggested that these mutations are associated with a poorer response to treatment,” said Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “It was therefore encouraging to see in this exploratory analysis that Keytruda monotherapy was associated with a survival benefit in certain patients with metastatic nonsquamous non-small cell lung cancer, regardless of KRAS mutational status.”

The objective of the exploratory analysis was to assess the prevalence of KRAS mutations and their association with efficacy in the KEYNOTE-042 trial. Of the 1,274 untreated patients with metastatic nonsquamous NSCLC whose tumors expressed PD-L1 (TPS ≥1%) enrolled in KEYNOTE-042, 301 patients had KRAS evaluable data (n=232 without any KRAS mutation; n=69 with any KRAS mutation, including n=29 with the KRAS G12C mutation).

Tissue tumor mutational burden (tTMB) and KRAS mutational status were determined by whole-exome sequencing (WES) of tumor tissue and matched normal DNA (blood). Patients were randomized 1:1 to receive Keytruda 200 mg intravenously every three weeks (n=637) or investigator’s choice of chemotherapy (pemetrexed or paclitaxel) (n=637). Treatment continued until progression of disease or unacceptable toxicity. The primary endpoint was OS with a TPS of ≥50%, ≥20% and ≥1%, which were assessed sequentially. The secondary endpoints were PFS and ORR.

Findings from this exploratory analysis showed that Keytruda monotherapy was associated with improved clinical outcomes, regardless of KRAS mutational status, in patients with metastatic nonsquamous NSCLC versus chemotherapy. In this analysis, Keytruda reduced the risk of death by 58% (HR=0.42 [95% CI, 0.22-0.81]) in patients with any KRAS mutation and by 72% (HR=0.28 [95% CI, 0.09-0.86]) in patients with the KRAS G12C mutation compared to chemotherapy.


Venetoclax in reduced-intensity transplant conditioning regimen in high-risk myeloid cancers shows promise

For patients with high-risk myeloid cancers undergoing a donor stem cell transplant, adding the targeted drug venetoclax to a reduced-intensity drug regimen prior to transplant is safe and does not impair the ability of the donor cells to take root in recipients’ bodies, a study led by Dana-Farber Cancer Institute researchers suggests.

The study was presented at the 61st American Society of Hematology annual meeting.

The findings provide support for the use of venetoclax prior to transplant as a way to increase the chances of transplant success in this group of patients, said Jacqueline S. Garcia, physician in the Adult Leukemia Program at Dana-Farber and first author of the study.

While a donor stem cell transplant can cure myeloid malignancies such as acute myeloid leukemia and myelodysplastic syndrome, patients whose tumor cells carry certain genetic mutations or chromosomal abnormalities have a high risk of relapsing after transplant. A variety of approaches to lowering the chance of relapse are under study. One involves using venetoclax, which prompts cancer cell death by blocking the BCL-2 protein, as part of the conditioning regimen patients receive in preparation for a donor stem cell transplant.

The new study focused on patients who underwent reduced-intensity conditioning regimens, which use lower, less toxic doses of chemotherapy and radiation therapy. While such regimens kill fewer cancer cells than traditional “myeloablative” treatments, they are milder on the body and are used in patients over age 60.

“In previous research, we have shown that adding venetoclax to leukemia drugs produces a very large increase in anti-leukemia activity,” Garcia remarked. “We hypothesized that venetoclax would promote the anti-leukemic effect of conditioning chemotherapy and therefore reduce the risk of relapse without producing undue toxicity.”

The study involved nine patients with high-risk AML or MDS who were recommended for a donor stem cell transplant. In a phase I clinical trial, they received venetoclax along with the chemotherapy drugs fludarabine and busulfex as a conditioning regimen and then underwent a donor stem cell transplant.

“We found that venetoclax can be safely added to standard reduced-intensity conditioning without impeding the ability of donor neutrophils [a type of white blood cell] to engraft,” Garcia stated.

Because patients are just six months removed from transplant, it is too early to know if the new regimen reduced the chance of relapse, Garcia noted, but the fact that the donor cells have engrafted—evidenced by patients’ blood counts—is an encouraging sign. There has not been a signal of toxicity in excess of what is expected with standard reduced-intensity conditioning, including rates of graft-versus-host disease. To further minimize the potential for relapse, the trial is under an amendment to allow trial participants to receive post transplant maintenance therapy of low dose venetoclax and the chemotherapy drug azacytidine.

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