Adding the anti-CD20 monoclonal antibody rituximab (various brands) to induction chemotherapy in patients with B-precursor acute lymphoblastic leukaemia (B-ALL) does not improve outcomes, UK researchers have found in a primary analysis of phase 3 trial data.
However, a separate examination of findings from the same study may nevertheless point to an update to the genetic classification for the disease that could help in creating an overall combined clinical and genetic risk score.
The research was published as an abstract from the British Society for Haematology 60th Annual Scientific Meeting, which was cancelled due to the COVID-19 pandemic.
UKALL14 involved patients with B-ALL aged 2565 years, regardless of Philadelphia chromosome (Ph) status or CD20 expression, who were randomised to standard induction chemotherapy (SOC) with or without 4 doses of rituximab (SOC+R).
Focusing on patients recruited after an amendment to the SOC regimen in April 2012, the team conducted an intention-to-treat analysis in 288 SOC patients and 289 given SOC+R, of whom 95.5% received all 4 doses of the immunotherapy.
Adele Fielding, professor of haematology at University College London Cancer Institute, London, and colleagues report that complete remission rates, at 92.7% with SOC and 94.8% with SOC+R, were similar in the two treatment arms.
There was also no difference in minimal residual disease (MRD) rates, with 42.2% and 41.8%, respectively, negative for residual disease.
Adverse, including severe, event rates were similar between the two cohorts, and there was no difference in non-relapse mortality.
After a median follow-up of 50.5 months, the researchers calculate that the 3-year event-free survival (EFS) for patients given SOC was 41.9% versus 48.7% for those receiving SOC+R, at a hazard ratio of 0.88 (p=0.28).
This contrasts with the French GRAALL-2005/R study, in which adults aged 1859 years with CD20-positive, Phnegative ALL were randomised to chemotherapy with or without rituximab, with a total of 16 to 18 infusions given across all treatment phases.
Their results indicated that adding rituximab to the ALL chemotherapy protocol improved outcomes, increasing EFS by 33% versus chemotherapy alone (p=0.04).
Prof Fielding told Medscape News UK that, for UKALL14, they had "hypothesised that giving rituximab early would make the difference, namely in helping to eliminate MRD early on".
"We were anxious not to give too much in case of toxicity from infections. It turned out that it is not toxic and doesnt seem to work to eliminate MRD early on."
She added that, in fact, "the French data showed that too," which prompts her to wonder at the mechanism of action of rituximab in B-ALL.
"Maybe you need more doses at times when patients have functional neutrophils or macrophages, or natural killer cells."
Prof Fielding also pointed out that, in the French study, they focused on patients with Ph-negative disease and in those in whom more than 20% of blasts expressed CD20.
"An important finding from our workis that the level of CD20 expression does not correlate with response to rituximab."
Approached for comment, Rachel Kahn, research communications manager at Blood Cancer UK, said that, "the immunotherapy drug rituximab remains a vital treatment for many types of blood cancer".
She told Medscape News UK, however, that "this interesting research suggests that there may not be any additional benefit of taking this drug for people with ALL".
She highlighted that the results nevertheless suggested that patients who underwent myeloablative allogeneic stem cell transplant (MAallaSCT) appeared to derive a significant benefit from adding rituximab to SOC.
Three-year EFS was 50.7% among MAallaSCT patients given SOC alone versus 72.2% in those receiving SOC+R, at a hazard ratio of 0.47 (p=0.03), which was related to a reduction in relapse risk.
This effect was not seen in patients given reduced intensity allogeneic stem cell transplantation or in maintenance groups, prompting Rachel Kahn to call for further research to identify which patients with ALL "may benefit from taking rituximab".
Prof Fielding said that, as they "do not have any plausible biological explanation" for the finding, the team is "going to be cautious about interpreting" it.
Overall, she feels that, as rituximab is "safe, its probably better to give it to everyone", as "our ability to do that is greater than our ability to do proper flow cytometry in local centres to accurately quantify CD20".
In a separate analysis, Prof Fielding and colleagues looked at all 653 patients who started treatment both before and after the SOC regimen amendment, of whom 49% were found to have high-risk chromosomal abnormalities.
These included 31% with BCR-ABL1, 8% with KMT2A-AFF1, 9% with HoL and 5% with CK abnormalities.
CK and HoL patients had lower 3-year overall survival than the overall cohort, at 24% and 19%, respectively, versus 52%, while patients with KMT2A-AFF1 fusion had an overall survival of 44% and BCR-ABL1 patients had a similar survival to the overall group.
The team also identified a series of other chromosomal abnormalities, including 1.3% with ABL-class fusions and the same proportion with JAK-STAT abnormalities, the latter had reduced 3-year overall survival, at 35%.
In contrast, among the 3% of patients with ZNF384 fusions, only two relapsed and none died.
Having found that secondary copy number alterations affecting key genes had no impact on outcomes, the team proposed "an amendment to the genetic risk classification for adult ALL", consisting of:
very high risk: CK, HoL or JAK-STAT abnormalities
high risk: all KMT2A fusions
tyrosine kinase sensitive: BCR-ABL1 and ABL-class fusions
low-risk: ZNF384 fusions
standard risk: all other patients
The team writes: "The integration of these primary genetic risk factors with other risk factors such as age, white cell count and MRD into an overall risk score is a key goal of our current work."
Prof Fielding said that the "immediate goal" of the team is "evaluating an overall risk score in our next trial, UKALL15, which has been submitted to Cancer Research UK for funding".
Rachel Kahn commented that "this research is a key example of how important it is to continue developing risk scores based on the make-up of the cancer, which can help clinicians understand how likely someone is to respond to treatment".
"This study shows that further clues can be found based on changes to a patients chromosomes."
She continued: "The more we know about how abnormalities influence how risky a cancer is thought to be, the closer we get to being able to personalise treatment to each individual to give them the most effective treatments and the best possible chance of survival."
The study was funded by Cancer Research UK.
No conflicts of interest declared.
[However, Fielding declared to ASH : Amgen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Incyte: Consultancy.
BSH 2020: Abstracts BSH2020-OR-001 & BSH2020-OR-004
Read the original post:
- Researchers find that fish oil may help with depression - Jill Lopez - July 16th, 2020
- How frogs became green again, and again, and again : Research Highlights - Nature.com - July 16th, 2020
- Pressing ahead - PharmaTimes - July 16th, 2020
- Citius Pharmaceuticals Brings on Myron S. Czuczman, MD as Chief Medical Officer (CMO) and Executive Vice President - PRNewswire - July 16th, 2020
- Global thirst for electricity is fuelling the rise of a potent greenhouse gas - Nature.com - July 6th, 2020
- Check it Out: Beat summer boredom by reading a book - The Columbian - July 6th, 2020
- Cell Separation Technology Market by Leading Manufacturers, Demand and Growth Overview 2019 to 2027 - Jewish Life News - July 4th, 2020
- Its not just the lungs COVID-19 can affect the brain and heart of those infected, researchers say - FOX 10 News Phoenix - July 1st, 2020
- Adult Stem Cells // Center for Stem Cells and Regenerative ... - July 1st, 2020
- Label-free sensing of exosomal MCT1 and CD147 for tracking metabolic reprogramming and malignant progression in glioma - Science Advances - June 30th, 2020
- Novel coronavirus infection might trigger type-1 diabetes - The Hindu - June 30th, 2020
- Recovering from Cancer, a Stem Cell Transplant and Coronavirus - Cancer Health Treatment News - June 30th, 2020
- FDA Approves Merck's KEYTRUDA (pembrolizumab) for the Treatment of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) that... - June 30th, 2020
- Century Therapeutics Announces Acquisition of Empirica Therapeutics - Business Wire - June 30th, 2020
- Century Therapeutics Announces Acquisition of Empirica Therapeutics | DNA RNA and Cells | News Channels - PipelineReview.com - June 23rd, 2020
- BrainStorm Cell Therapeutics to Join the Russell 2000 Index and Russell 3000 Index - PRNewswire - June 23rd, 2020
- Acute Myeloid Leukemia (AML) Therapeutics Market Promising Growth Opportunities over 2017 2025 - 3rd Watch News - June 23rd, 2020
- UK Startup Bags 37M to Remove Cell Therapy Manufacturing... - Labiotech.eu - June 16th, 2020
- EHA25Virtual: Adult Patients With Sickle Cell Disease May Be at Increased Risk of Adverse Outcomes From COVID-19 - Yahoo Finance - June 16th, 2020
- CRISPR Therapeutics and Vertex Announce New Clinical Data for Investigational Gene-Editing Therapy CTX001 in Severe Hemoglobinopathies at the 25th... - June 16th, 2020
- BrainStorm to Present at the Raymond James Human Health Innovations Conference - PRNewswire - June 12th, 2020
- Mesenchymal Stem Cells Market - Advances & Applications scrutinized in the new analysis - WhaTech Technology and Markets News - June 12th, 2020
- Autolus Therapeutics presents AUTO1 and AUTO3 data at the 2020 EHA25 Virtual Congress - BioSpace - June 12th, 2020
- Genmab Announces European Marketing Authorization for the Subcutaneous Formulation of DARZALEX (daratumumab) for the Treatment of Patients with Multi... - June 12th, 2020
- Stem Cell Therapy Seen to Help COPD Patients with Severe Inflammation - COPD News Today - June 8th, 2020
- Stem Cells Market Analytical Overview, Growth Factors, Demand and Trends Forecast to 2028 - News Collective - June 8th, 2020
- Stem Cell Assay Market-Top Companies, Business Growth And Investment Opportunities, Share and Forecasts 2025 - Jewish Life News - June 8th, 2020
- Creating hairy human skin: Not as easy as you think - Science Codex - June 8th, 2020
- Global Stem Cells Market 2020 (COVID-19) Impact Analysis: Business Trends, Growth Insight, Statistics And Forecast to 2025 - Surfacing Magazine - June 8th, 2020
- Ide-cel Appears Active in Almost Three-Fourths of Heavily Pretreated Patients with Myeloma - Cancer Network - June 8th, 2020
- Study reveals birth defects caused by flame retardant - University of Georgia - June 8th, 2020
- Buckeye butterflies get their color from their scales - Massive Science - June 3rd, 2020
- Gracell Announces Two Presentations at the Annual Meeting of American Society of Clinical Oncology (ASCO) - PRNewswire - May 31st, 2020
- Stem cell treatments elicit full structural regeneration of the sun-aged skin - News-Medical.Net - May 29th, 2020
- AgeX Therapeutics and Sernova to Collaborate to Engineer Universal Locally Immune Protected Cell Therapies for Type I Diabetes and Hemophilia A -... - May 29th, 2020
- Genmab Announces Positive Topline Results in Phase III ANDROMEDA Study of Daratumumab in Light-chain (AL) Amyloidosis - Financialbuzz.com - May 29th, 2020
- Opdivo + Yervoy receive FDA approval combined with limited chemotherapy as first-line treatment of metastatic or recurrent NSCLC - The Cancer Letter - May 29th, 2020
- AUGUSTMAN Grooming Awards 2020 Part IV: Best Head-To-Toe Treatment Services For Gentlemen - AUGUSTMAN - May 29th, 2020
- Merck's KEYTRUDA (pembrolizumab) Superior to Standard of Care Chemotherapy in Patients with MSI-H Colorectal Cancer - BioSpace - May 29th, 2020
- KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination Demonstrated Clinically Meaningful Tumor Response Rates in Unresectable Hepatocellular... - May 29th, 2020
- Canine Stem Cell Therapy Market Covid-19 Impact In 2026 | In-depth Analysis, Global Market Share, Top Trends, Professional & Technical Industry... - May 27th, 2020
- Looking toward the Future of Cell & Gene Therapies - Genetic Engineering & Biotechnology News - May 27th, 2020
- Past ISP Projects, School of Medcine - UC San Diego Health - May 27th, 2020
- Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy | DNA RNA and Cells | News Channels - PipelineReview.com - May 27th, 2020
- Immunotherapy Drug Market Global Trends, Market Share, Industry Size, Growth, Opportunities, and Market Forecast 2020 to 2025 - 3rd Watch News - May 27th, 2020
- Incyte and MorphoSys Announce the Validation of the European Marketing Authorization Application for Tafasitamab - Business Wire - May 21st, 2020
- Mesoblast: Recruitment Commenced For NIH Supported Phase 2/3 Trial Of Remestemcel-L In COVID-19 Acute Respiratory Distress Syndrome - Seeking Alpha - May 21st, 2020
- Dose-dependent functions of SWI/SNF BAF in permitting and inhibiting cell proliferation in vivo - Science Advances - May 21st, 2020
- Adult Stem Cells 101 Boston Children's Hospital - May 16th, 2020
- Revealed: First trial of pioneering stem-cell treatment for heart disease performed in China - Nature.com - May 14th, 2020
- Adult Stem Cells - May 14th, 2020
- Dlp-mediated Hh and Wnt signaling interdependence is critical in the niche for germline stem cell progeny differentiation - Science Advances - May 14th, 2020
- CTX001 for Treatment of Sickle Cell Disease and Other Blood Disorders - Sickle Cell Anemia News - May 14th, 2020
- Australia's Mesoblast raises $90M to scale up stem cell therapy manufacturing to treat COVID-19 ARDS - BioWorld Online - May 14th, 2020
- Stem cells therapy A prospective treatment against coronavirus? - Daily Excelsior - May 14th, 2020
- Merck's KEYTRUDA (pembrolizumab) Superior to Brentuximab Vedotin (BV), a Standard of Care, in Patients With Classical Hodgkin Lymphoma (cHL) in... - May 14th, 2020
- Adult Stem Cell - an overview | ScienceDirect Topics - May 12th, 2020
- Altered Bone Marrow Microenvironment Induces Defect of Hematopoietic Stem Cells in -thalassemia - Hematology Advisor - May 12th, 2020
- Stemline Slated for Acquisition by Menarini in Deal Worth Up to $677M - Xconomy - May 9th, 2020
- Region 3: Immune and Cellular Tx, Part II - MedPage Today - May 9th, 2020
- Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome - The Lancet - May 9th, 2020
- BrainStorm Leases a New Cleanroom Facility at The Tel Aviv Sourasky Medical Center to Manufacture NurOwn for The European Union - StreetInsider.com - May 9th, 2020
- Weekly pick of brain tumour research news from around the world - Brain Tumour Research - May 9th, 2020
- BrainStorm Leases a New Cleanroom Facility at The Tel Aviv Sourasky Medical Center to Manufacture NurOwn for The European Union - BioSpace - May 7th, 2020
- Here's Why Athersys Tumbled 23.3% in April - The Motley Fool - May 7th, 2020
- What is the Value of iPSC Technology in Cardiac... - The Doctor Weighs In - May 7th, 2020
- Schizophrenia drug points to improved brain cancer radiation therapy - New Atlas - May 7th, 2020
- Merck to Present New Data from its Broad Oncology Portfolio and Pipeline at the ASCO20 Virtual Scientific Program - Maryville Daily Times - May 7th, 2020
- What Do New Neurons in the Brains of Adults Actually Do? - The Scientist - May 7th, 2020
- Scientists finally explained one of the strangest coronavirus symptoms - BGR - May 7th, 2020
- Teva and Celltrion Healthcare Announce the Launch of TRUXIMA (rituximab-abbs) Injection for Rheumatoid Arthritis, the Only Biosimilar to Rituxan... - May 7th, 2020
- Genmab Announces U.S. FDA Approval of Subcutaneous Formulation of Daratumumab, DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), for the Treatment... - May 3rd, 2020
- CHMP Issues Positive Opinion Recommending Subcutaneous Formulation of Daratumumab for the Treatment of Patients with Multiple Myeloma - Yahoo Finance - May 1st, 2020
- BrainStorm-Cell Therapeutics to Announce First Quarter Financial Results and Provide a Corporate Update - StreetInsider.com - May 1st, 2020
- Adult Stem Cells | HowStuffWorks - April 30th, 2020
- Adult stem cell - Wikipedia - April 30th, 2020
- Stem Cell Basics IV. | stemcells.nih.gov - April 30th, 2020
- Where Do We Get Adult Stem Cells? - Children's Hospital - April 30th, 2020
- Chimerix Announces Initiation of a Phase 2/3 Study of DSTAT in Acute Lung Injury for Patients with Severe COVID-19 - StreetInsider.com - April 29th, 2020
- US bishop: We must halt development of any coronavirus vaccine derived from aborted babies - Lifesite - April 29th, 2020