Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA)

Author(s): Emmanuel Bachy , MD, PhD^1,2; Vincent Camus , MD³; Catherine Thieblemont , MD, PhD⁴; David Sibon , MD, PhD⁵; René-Olivier Casasnovas , MD⁶; Loïc Ysebaert , MD, PhD⁷; Gandhi Damaj, MD, PhD⁸; Stéphanie Guidez, MD⁹; Gian Matteo Pica, MD¹⁰; Won Seog Kim , MD, PhD¹¹; Soon Thye Lim, MBBS¹²; Marc André, MD¹³; Alejandro Martín García-Sancho , MD, PhD¹⁴; Maria Jesus Penarrubia , MD, PhD¹⁵; Philipp B. Staber , MD, PhD¹⁶; Judith Trotman , MBChB¹⁷; Andreas Hüttmann , MD¹⁸; Vittorio Stefoni, MD, PhD¹⁹; Alessandro Re, MD²⁰; Philippe Gaulard , MD²¹; Marie-Helene Delfau-Larue, MD, PhD²²; Laurence de Leval, MD, PhD²³; Michel Meignan , MD, PhD²⁴; Ju Li, PhD²⁵; Franck Morschhauser , MD, PhD²⁶; and Richard Delarue, MD^5,27;

Source: DOI: 10.1200/JCO.21.01815 Journal of Clinical Oncology 40, no. 3 (January 20, 2022) 242-251. Published online November 29, 2021. PMID: 34843406

Dr. Lucio Gordan's Thoughts

Unfortunately, another negative study of a drug being accretive to CHOP regimen in T-cell NHL. Newer drugs and concepts hopefully will move the needle in this decade.

PURPOSE

Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP).

METHODS

This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m2, was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria.

RESULTS

Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 (P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% (P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%).

CONCLUSION

The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL.

Author Affiliations

¹Hospices Civils de Lyon, Lyon, France ²Claude Bernard Lyon 1 University, Lyon, France ³Department of Hematology, Centre Henri Becquerel, Rouen, France ⁴APHP, Hôpital Saint-Louis, Service d’hémato-oncologie, DMU DHI, Université de Paris, Paris, France ⁵Service d’Hématologie adultes, Hopital Universitaire Necker Enfants Malades, AP-HP, Paris, France ⁶Department of Hematology, CHU Dijon-Bourgogne and INSERM 1231, Dijon, France ⁷IUCT Oncopole, Toulouse, France ⁸Hematology Institute, University Hospital, Normandy University, School of Medicine, Caen, France ⁹Service d’Hématologie, CHU de Poiters, Poiters, France ¹⁰Department of Hematology, Centre Hospitalier Métropole Savoie Chambéry, Chambéry, France ¹¹Samsung Medical Center, Seoul, South Korea ¹²National Cancer Centre Singapore, Singapore ¹³Department of Hematology, CHU UCL Namur, Yvoir, Belgium ¹⁴Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain ¹⁵Hospital Clinico Universitario de Valladolid, Valladolid, Spain ¹⁶Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria ¹⁷Concord Repatriation General Hospital, University of Sydney, Concord, Australia ¹⁸Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ¹⁹Policlinico Sant’Orsola-Malpighi, Bologna, Italy ²⁰Hematology Division, Spedali Civili di Brescia, Brescia, Italy ²¹Department of Pathology and Inserm U955, University Hospital Henri Mondor, Créteil, France ²²Department of Immunobiology and Inserm U955, Université Hôpital Henri Mondor, Créteil, France ²³Institute of Pathology, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland ²⁴LYSA Imaging, APHP, Hôpital Henri Mondor, Université Paris Est, Créteil, France ²⁵Bristol Myers Squibb Company, Princeton, NJ ²⁶Univ. Lille, CHU Lille, ULR 7365 – GRITA – Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille, France ²⁷Celgene, a Bristol Myers Squibb Company, Boudry, Switzerland

A phase 2 trial of CHOP with anti-CCR4 antibody mogamulizumab for older patients with adult T-cell leukemia/lymphoma Available to Purchase

The phase 2 trial of Moga-CHOP (CHOP + mogamulizumab) in older patients with aggressive adult T-cell leukemia/lymphoma (ATL) demonstrated a significant improvement in 1-year PFS (36.2% vs 16% historical control), with a 1-year OS of 66.0% and a CR rate of 64.6%. The overall response rate (ORR) was high at 91.7%, and the median overall survival (OS) reached 1.6 years. Notably, CCR4 mutations and Moga-associated cutaneous AEs correlated with better OS, and the regimen was generally tolerable with no unexpected toxicities. Bottom line: Moga-CHOP is now a strong first-line option for older, transplant-ineligible ATL patients, and it’s encouraging to see these survival gains in a population with historically poor outcomes.

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor–Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)

Pirtobrutinib improved progression-free survival (PFS) to 14 months compared to 8 months with Idelalisib/Rituximab or Bendamustine/Rituximab (IdelaR/BR), with a hazard ratio of 0.54, in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously been treated with covalent BTK inhibitors (cBTKi). It also demonstrated favorable tolerability. With acalabrutinib and venetoclax emerging as preferred first-line therapies, Pirtobrutinib represents a strong second-line option for eligible patients.

Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma

The ECHELON-3 study showed BV + Len + R is an active and (relatively) tolerable in the rrDLBCL patient group. Interestingly, patients did not have to be CD30+ to see a benefit.

Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma

For transplant-eligible patients with Mantle Cell Lymphoma, Obinutuzumab showed superior efficacy compared to Rituximab. These patients are uncommon, but the results of this study show that in this context O seems to beat R in every aspect, including a 5-yr PFS of 82.8 vs 66.6%, which is striking. I would consider this option for the appropriate patient.

Ibrutinib and venetoclax as primary therapy in symptomatic, treatment-naïve Waldenström macroglobulinemia

This combination had impressive results but led to a high rate of ventricular arrythmias (9%), hence the combination is not recommended. Another study with the combination and rituximab was also suspended, the etiology of the higher rate of Vent arrhythmias is not known. This combination in another lymphoid malignancies did not lead to that rate of toxicity.