CAR-T for second line is better than standard of care, the question is: how about compared to BITE therapy? Future is exciting for those patients.
Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL
Addition of oral azacitidine to CHOP as initial therapy is safe, and induces high rates of CR in patients with PTCL-TFH. Integrative analyses suggest that azacitidine priming promotes apoptosis and inflammation within the lymphoma tumor microenvironment.
Peripheral T-cell lymphomas (PTCL) with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as initial treatment for PTCL. CC-486 at 300 mg daily was administered for 7 days before C1 of CHOP, and for 14 days before CHOP C2-6. The primary end point was end-of-treatment complete response (CR). Secondary end points included safety and survival. Correlative studies assessed mutations, gene expression, and methylation in tumor samples. Grade 3 to 4 hematologic toxicities were mostly neutropenia (71%), with febrile neutropenia uncommon (14%). Nonhematologic toxicities included fatigue (14%) and gastrointestinal symptoms (5%). In 20 evaluable patients, CR was 75%, including 88.2% for PTCL-TFH (n = 17). The 2-year progression-free survival (PFS) was 65.8% for all and 69.2% for PTCL-TFH, whereas 2-year overall survival (OS) was 68.4% for all and 76.1% for PTCL-TFH. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 76.5%, 41.1%, 23.5%, and 23.5%, respectively, with TET2 mutations significantly associated with CR (P = .007), favorable PFS (P = .004) and OS (P = .015), and DNMT3A mutations associated with adverse PFS (P = .016). CC-486 priming contributed to the reprograming of the tumor microenvironment by upregulation of genes related to apoptosis (P < .01) and inflammation (P < .01). DNA methylation did not show significant shift. This safe and active regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL. This trial was registered at www.clinicaltrials.gov as #NCT03542266.
Author AffiliationsJia Ruan1;Alison Moskowitz2;Neha Mehta-Shah3;Lubomir Sokol4Zhengming Chen1;Nikita Kotlov5;Grigorii Nos5;Maria Sorokina5;Vladislav Maksimov5;Andrea Sboner1;Michael Sigouros1;Koen van Besien1;Steven Horwitz2;Sarah C. Rutherford1;Erin Mulvey1;Maria V. Revuelta1;Jenny Xiang1;Alicia Alonso1;Ari Melnick1;Olivier Elemento1;Giorgio Inghirami1;John P. Leonard1;Leandro Cerchietti1;Peter Martin1
Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170
Pembrolizumab in lymphoma, this is not a common one, usually in young females, could be hard to treat.
Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma
5-year survival data from the Zuma trials shows that there is curative potential in r/r DLBCL with cure rates near 50%.
Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial
Is ibrutininb’s days as a treatment for CLL over? Zanubrutinib is more effective and less toxic.
This is not a trial, but really a very nice review article, too. A good read especially as we may start prescribing those meds locally.