Onco-hematology
RCT: Ponatinib shows superior MRD-negative complete remission rates compared to Imatinib in newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia – JAMA
25 May, 2024 | 19:03h | UTCThis global phase 3 randomized clinical trial investigated the efficacy and safety of ponatinib versus imatinib in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The study, conducted across 77 sites, enrolled 245 patients who were randomized in a 2:1 ratio to receive either ponatinib (30 mg/d) or imatinib (600 mg/d) alongside reduced-intensity chemotherapy. The primary endpoint of the trial was minimal residual disease–negative (MRD-negative) complete remission, assessed at the end of cycle 3. Results showed that ponatinib achieved a significantly higher MRD-negative complete remission rate of 34.4% compared to 16.7% with imatinib. Additionally, the safety profile between the two drugs was comparable, with arterial occlusive events being rare and similar across groups. These findings suggest ponatinib as a potentially preferable frontline therapy in this patient population due to its superior efficacy in achieving MRD-negative status without compromising safety.
Reference (link to abstract – $ for full-text):
RCT: Adding Ibrutinib to immunochemotherapy and autologous stem-cell transplantation improves PFS in young mantle cell lymphoma patients but increases toxicity – The Lancet
5 May, 2024 | 15:02h | UTCStudy Design and Population:
This study is a three-arm, randomized, open-label, phase 3 superiority trial named TRIANGLE, conducted across 165 centers in Europe and Israel. It aimed to compare the effectiveness of adding ibrutinib to standard immunochemotherapy, both with and without autologous stem-cell transplantation (ASCT), in 870 previously untreated mantle cell lymphoma patients aged 18-65 years, suitable for ASCT.
Main Findings:
After a median follow-up of 31 months, the arm with ibrutinib added to immunochemotherapy followed by ASCT (group A+I) demonstrated a 3-year failure-free survival rate of 88% compared to 72% in the standard immunochemotherapy plus ASCT group (group A). This indicates a significant improvement (hazard ratio 0.52; p=0.0008). Conversely, the efficacy of ASCT in the presence of ibrutinib (group A+I vs. group I, ibrutinib without ASCT) remains under analysis. Adverse events were more frequent and severe post-ASCT, particularly concerning hematological complications and infections.
Implications for Practice:
The results suggest that adding ibrutinib to first-line immunochemotherapy regimens significantly enhances clinical outcomes in younger patients with mantle cell lymphoma. However, the increased toxicity observed warrants careful patient monitoring, especially following ASCT. Further research is needed to evaluate the necessity and timing of ASCT in regimens containing ibrutinib.
Reference (link to free full-text):
Systematic Review: Daratumumab enhances survival in newly diagnosed multiple myeloma patients ineligible for transplant – Cochrane Library
4 May, 2024 | 13:46h | UTCStudy Design and Population:
This Cochrane review evaluates four open-label, two-arm randomized controlled trials involving 1,783 adults with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant. The studies were conducted globally, mainly in middle- and high-income countries, with participants aged between 69 to 74 years. Adding Daratumumab, a CD38-targeting monoclonal antibody, to standard antineoplastic therapy was compared to standard antineoplastic therapy alone.
Main Findings:
Daratumumab significantly improved overall survival with a hazard ratio of 0.64 and increased progression-free survival with a hazard ratio of 0.48, based on moderate-certainty evidence from the studies. Quality of life showed a slight improvement, although the evidence was of low certainty. Treatment-related serious adverse events were more common in the daratumumab group, with a risk ratio of 1.18. However, there was no significant increase in adverse events of CTCAE grade ≥3, except for a higher risk of infections.
Implications for Practice:
The addition of daratumumab to standard antineoplastic therapy offers a potential benefit in overall survival and disease progression control for patients with multiple myeloma who are ineligible for transplant. These benefits must be weighed against the increased risk of serious adverse events and infections. Future studies could provide further insights, particularly into the long-term quality of life and management of side effects.
Reference (link to abstract – $ for full-text):
RCT | Early oral antibiotic switch in low-risk neutropenic sepsis shows mixed results
3 Aug, 2023 | 13:15h | UTC
Phase 1 Trial | NI006 shows potential for cardiac amyloid depletion in transthyretin amyloid cardiomyopathy
1 Aug, 2023 | 14:17h | UTCPhase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid – New England Journal of Medicine (link to abstract – $ for full-text)
Commentaries:
Amyloid Removal Looks Possible in ATTR Cardiomyopathy Imaging Trial – TCTMD
Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid – American College of cardiology
Phase 1–2 study | Liso-cel shows effectiveness against resistant CLL/SLL post BTK inhibitor, venetoclax treatment
20 Jul, 2023 | 10:58h | UTCLisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1–2 study – The Lancet (link to abstract – $ for full-text)
News Release: Immunotherapy Improves Remission for Relapsed, Refractory Leukemia – Northwestern Medicine
Review | Guiding the use of invasive cardiac interventions in patients with advanced malignancies
17 Jul, 2023 | 13:23h | UTC
Clinical Trial Update | 5-year follow-up validates efficacy of sorafenib maintenance in FLT3-ITD AML
11 Jul, 2023 | 13:37h | UTCSorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial – The Lancet Haematology (link to abstract – $ for full-text)
Commentary on Twitter
NEW: with over 5 years of follow-up, sorafenib maintenance is associated with improved outcomes compared w/ non-maintenance in patients w/ FLT3-ITD AML undergoing allogeneic HSCT in a multicentre, randomised, ph 3 trial #leusm #bmtsm https://t.co/JK190vS0Ql pic.twitter.com/SBP887hgEu
— The Lancet Haematology (@TheLancetHaem) July 5, 2023
Single-arm study | Pirtobrutinib exhibits efficacy in CLL patients after failure of covalent BTK inhibitor treatment
7 Jul, 2023 | 16:14h | UTCPirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia – New England Journal of Medicine (link to abstract – $ for full-text)
News release from the manufacturer: New England Journal of Medicine Publishes BRUIN Phase 1/2 Trial Data for Pirtobrutinib in BTK Inhibitor Pre-Treated Adult Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma – Lilly
Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management
5 Jul, 2023 | 01:00h | UTC
SR | Polyclonal anti‐thymocyte globulins for the prophylaxis of GVHD after allogeneic stem cell or bone marrow transplantation
3 Jul, 2023 | 14:16h | UTC
RCT | Luspatercept outperforms epoetin alfa in interim analysis, shows promise for lower-risk myelodysplastic syndromes
30 Jun, 2023 | 14:42h | UTCEfficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial – The Lancet (link to abstract – $ for full-text)
RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation
27 Jun, 2023 | 13:54h | UTCSummary: The article details a phase 3 trial comparing the efficacy of two graft-versus-host disease (GVHD) prophylactic regimens in hematologic cancer patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). The experimental group received cyclophosphamide–tacrolimus–mycophenolate mofetil, and the standard group received tacrolimus–methotrexate. The patients, a total of 431, underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor.
The primary end point was GVHD-free, relapse-free survival at 1 year. Results indicated a significantly higher incidence of this outcome in the experimental group (hazard ratio, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) in the experimental group, compared to 34.9% (95% CI, 28.6 to 41.3) in the standard group.
Notably, patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall survival, disease-free survival, relapse, transplantation-related death, and engraftment did not show a substantial difference between the groups. These results suggest that cyclophosphamide–tacrolimus–mycophenolate mofetil may offer a more effective prophylaxis against GVHD in HSCT patients.
Article: Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant – Johns Hopkins Medicine
Commentary on Twitter
In this trial, 1-year GVHD-free, relapse-free survival after stem-cell transplantation was 52.7% in the cyclophosphamide–tacrolimus–mycophenolate mofetil group and 34.9% in the tacrolimus–methotrexate group. https://t.co/wCdvP1LChu
— NEJM (@NEJM) June 21, 2023
Consensus Paper | Primary prophylaxis of invasive fungal diseases in patients with hematological malignancies
23 Jun, 2023 | 13:23h | UTC
Consensus Paper | Management of febrile neutropenia in pediatric hematology and oncology patients
20 Jun, 2023 | 12:38h | UTC
Review | Updates in immunohistochemistry for hematopoietic and lymphoid neoplasms
20 Jun, 2023 | 12:36h | UTC
RCT | Avapritinib superior to placebo in reducing symptoms, mast-cell burden in indolent systemic mastocytosis patients
20 Jun, 2023 | 12:34h | UTCAvapritinib versus Placebo in Indolent Systemic Mastocytosis – NEJM Evidence
Commentary on Twitter
“…in this 24-week blinded phase of the PIONEER trial, avapritinib demonstrated superiority to placebo in improving symptoms in patients with moderate to severe symptomatic ISM [indolent systemic mastocytosis]….”#Oncology #ClinicalTrials @StanfordDeptMed @ProfMaurer
— NEJM Evidence (@NEJMEvidence) June 15, 2023
Review | Antifungal stewardship interventions in patients with hematologic malignancies
16 Jun, 2023 | 13:47h | UTCAntifungal Stewardship Interventions in Patients with Hematologic Malignancies
RCT | Second-line treatment with Axi-cel results in increased overall survival in large B-cell lymphoma
14 Jun, 2023 | 14:25h | UTCSurvival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Late breaking at #ASCO23: In the phase 3 ZUMA-7 trial, patients with relapsed or refractory large B-cell lymphoma who received axi-cel (CD19-specific CAR T cells) had a 27.4% lower risk of death than patients who received standard therapy. Full trial results:
— NEJM (@NEJM) June 5, 2023
RCT | Cilta-cel shows superior progression-free survival over standard care in lenalidomide-refractory multiple myeloma
14 Jun, 2023 | 14:22h | UTCCilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Original Article: Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4) https://t.co/Wag2UTKOfH#ASCO23
— NEJM (@NEJM) June 6, 2023
Review | Acute graft-versus-host disease
14 Jun, 2023 | 14:20h | UTCAcute graft-versus-host disease – Nature Reviews Disease Primers (if the link is paywalled, try this one)
Commentary on Twitter
Tissue damage resulting from allogenic hematopoietic cell transplantation conditioning regimens triggers cellular interactions and #inflammatory cascades that lead to acute #GraftVersusHost disease symptoms https://t.co/iHyUVoV75J pic.twitter.com/ob9X7zQWB8
— Nature Reviews Disease Primers (@DiseasePrimers) June 11, 2023
RCT | Noninferiority shown between DOACs and LMWH for recurrent VTE prevention in cancer patients
5 Jun, 2023 | 13:50h | UTCSummary: This unblinded, pragmatic, noninferiority randomized clinical trial aimed to assess the efficacy of direct oral anticoagulants (DOACs) against low-molecular-weight heparin (LMWH) in preventing recurrent venous thromboembolism (VTE) in patients with cancer. The study included 671 patients from 67 oncology centers, with a new clinical or radiological diagnosis of VTE.
Participants were randomly assigned to receive either a DOAC or LMWH for 6 months, and treating physicians selected and prescribed the drugs based on considerations like availability and drug-drug interactions. The primary outcome was the rate of recurrent VTE at 6 months. Findings revealed that the DOAC group had a recurrent VTE rate of 6.1% as compared to 8.8% in the LMWH group, showing noninferiority. Both groups had statistically similar rates of major bleeding and severe adverse events.
This pragmatic study included patients with advanced cancer and brain metastases, impaired performance status, and reduced liver or kidney function, making it more representative of routine oncology practice. Moreover, patient adherence to DOAC treatment was significantly higher than to LMWH. Nevertheless, the study had limitations, including the lack of blinding and underrepresentation of certain racial and ethnic groups.
In conclusion, this trial suggests that DOACs were noninferior to LMWH for preventing recurrent VTE in patients with cancer over a 6-month follow-up period, supporting the use of DOACs in this population for VTE prevention. Further research is needed to confirm these results and investigate long-term outcomes.
Article: Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial – JAMA (free for a limited period)
See also: Visual abstract
Commentary on Twitter
Among adults with cancer and VTE, direct oral anticoagulants were noninferior to low-molecular-weight heparin for preventing recurrent VTE over 6-month follow-up. #ASCO23 https://t.co/DP5RvlSYxe pic.twitter.com/rBJ99plopK
— JAMA (@JAMA_current) June 2, 2023
Review | Prevention of venous thromboembolism in patients with cancer
5 Jun, 2023 | 13:48h | UTCPrevention of venous thromboembolism in patients with cancer – The BMJ
Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies
1 Jun, 2023 | 11:48h | UTC
RCT | Ruxolitinib achieves greater molecular response and EFS in hydroxycarbamide-resistant Polycythemia Vera
22 May, 2023 | 13:35h | UTCCommentary: Ruxolitinib Appears to Yields Superior Responses in Polycythemia Vera Subtype – Cancer Network