Background: Peripheral T-cell lymphoma (PTCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that is typically associated with a poor prognosis. Romidepsin is a histone deacetylase inhibitor ...approved by the US Food and Drug Administration for patients with PTCL who have received at least 1 prior therapy (J Clin Oncol. 2012;30:631). Presented here is the final analysis of a phase III randomized study comparing romidepsin + cyclophosphamide, doxorubicin, vincristine, and prednisone (Ro-CHOP) with CHOP in patients with previously untreated PTCL.
Methods: Ro-CHOP (NCT01796002) is a randomized multicenter phase III study in adult patients with previously untreated PTCL (i.e. nodal or extranodal entities including primary cutaneous non epidermotropic TCL, with the exclusion of ALK-positive anaplastic large cell lymphomas and EBV-positive extranodal NK/T-cell lymphomas). Diagnostic biopsies were centrally reviewed (94%), and patients were randomized based on International Prognostic Index (IPI) score at baseline (< 2 vs ≥ 2), age (≤ 60 vs > 60 y), and histology type (nodal vs extranodal) to receive either Ro-CHOP or CHOP. Two-sided P-value from log-rank test stratified by all 3 stratification factors was used. All patients received CHOP in 3-week cycles for 6 cycles. Romidepsin, 12 mg/m2, was administered intravenously on days 1 and 8 of each 3-week cycle for 6 cycles (Lancet Haematol. 2015;2:e160), with dose reductions to 10 and 8 mg/m2 based on toxicity. The primary end point was progression-free survival (PFS) per Response Adjudication Committee assessment according to International Working Group 1999 criteria. Secondary end points included overall survival (OS), objective response rate (ORR), complete response (CR) + CR unconfirmed (CRu), and safety.
Results: As of the December 13, 2019 cutoff date, 421 patients were included in the intention-to-treat population (Ro-CHOP, n = 211; and CHOP, n =210). Median age was 65 y (range, 25-81); 76 patients (18%) had ECOG PS of 2-3; 267 (63%) had Ann Arbor stage IV disease; and 342 (81%) had IPI score ≥ 2. At a median follow-up of 27.5 mo, the study did not meet its primary end point because Ro-CHOP did not show a statistically significant PFS improvement vs CHOP alone. Median PFS for Ro-CHOP vs CHOP was 12.0 mo (95% CI, 9.0-25.8) vs 10.2 mo (95% CI, 7.4-13.2), with a hazard ratio of 0.81 (95% CI, 0.63-1.04; P = 0.096). Median OS for Ro-CHOP vs CHOP was 51.8 mo (95% CI, 35.7-72.6) vs 42.9 mo (95% CI, 29.9-not evaluable). ORR of Ro-CHOP vs CHOP was 63% vs 60% with CR + CRu rates of 41% vs 37%. In the safety population (Ro-CHOP, n = 210; CHOP, n = 208), any-grade treatment emergent adverse events (TEAEs) that occurred ≥ 40% in the Ro-CHOP or CHOP arms, respectively, included anemia (67% vs 38%), nausea (55% vs 31%), thrombocytopenia (52% vs 17%), neutropenia (51% vs 37%), and vomiting (40% vs 10%). Grade 3/4 TEAEs that occurred in ≥ 30% of patients in the Ro-CHOP or CHOP arm, respectively, included thrombocytopenia (50% vs 10%), neutropenia (49% vs 33%), anemia (47% vs 17%), and leukopenia (32% vs 20%). One grade 5 TEAE occurred in the Ro-CHOP arm (E. coli sepsis), and 2 occurred in the CHOP arm (colitis and acute cholecystitis). In the Ro-CHOP vs CHOP arms, TEAEs led to CHOP dose interruption in 75 (36%) vs 42 (20%) patients, reduction in 54 (26%) vs 31 (15%) patients, and discontinuation in 7 (3%) and 6 (3%) patients, respectively. In the Ro-CHOP arm, TEAEs led to romidepsin interruption, reduction, and discontinuation in 132 (63%), 77 (37%), and 17 (8%) patients, respectively.
Conclusions: The addition of romidepsin to CHOP did not improve PFS, the primary endpoint of the study, and response rates and OS appeared similar with the combination. The toxicity profile of Ro-CHOP was consistent with its phase Ib/II data, with no unexpected findings. The high rates of TEAEs with the addition of romidepsin hampered the ability to adequately administer 6 cycles of CHOP. Additional exploratory analyses to compare Ro-CHOP outcomes in specific patient subgroups are ongoing. The combination of CHOP plus romidepsin does not represent an advance in the standard of care for patients with previously untreated PTCL.
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Bachy:Beigene: Membership on an entity’s Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Camus:PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria. Thieblemont:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Hospira: Research Funding; Incyte: Honoraria; Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: travel support; Bayer: Honoraria. Casasnovas:Amgen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy, Honoraria. Ysebaert:Roche: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; CELGENE: Honoraria; TAKEDA: Honoraria; JANSEN: Honoraria; AMGEN: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment. Kim:JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; Pfizer: Research Funding; F. Hoffmann-La Roche: Research Funding. Lim:National Cancer Centre Singapore: Current Employment. André:Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Novartis: Consultancy, Research Funding; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy; Celgene: Other, Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Martin Garcia-Sancho:Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Penarrubia Ponce:Novartis: Consultancy; Takeda: Consultancy, Honoraria; Janssen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Servier: Honoraria; HOSPITAL CLINICO UNIVERSITARIO DE VALLADOLID: Current Employment; Abbvie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy; Celgene: Consultancy, Honoraria; Incyte: Consultancy. Staber:msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Celgene/ BMS: Consultancy, Honoraria. Trotman:BeiGene: Research Funding; Takeda: Research Funding; F. Hoffmann-La Roche: Research Funding; Celgene: Research Funding; PCYC: Research Funding. Hüttmann:Takeda: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Seattle Genetics: Research Funding; Lead Discovery Center GmbH: Consultancy; Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria. Gaulard:Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); INNATE PHARMA: Research Funding; TAKEDA: Consultancy, Honoraria, Research Funding; CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment. Delfau-Larue:MUNDIPHARMA: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Honoraria; GILEAD: Honoraria; AMGEN: Honoraria. D
Introduction:
Given that there is no large case-series, effect of pregnancy on the course of pre-existing primary immune thrombocytopenia (ITP) patients is unclear1,2. Furthermore, outcome predictors ...evidence of neonates born to mothers with ITP is very scarce1. Due to obvious ethical reasons, no clinical trial regarding ITP and pregnancy has been reported until recent days3. Nevertheless, the relationship between ITP and pregnancy is considered a “trending topic” nowadays. As it is the, until now, unknown safety and efficacy of new drugs as TPO mimetics in this setting3-6.
Aims:
To evaluate outcome and global management of pregnancy and delivery on ITP women an on their offspring.
Methods:
Primary ITP was defined as a platelet count < 100 x 109/L in the absence of other causes or disorders that may be associated with thrombocytopenia.
All women diagnosed of primary ITP from 2011 to 2016 in 24 Spanish Hematology Departments who had at least one pregnancy after ITP onset were included in this registry.
Results:
We included 297 primary ITP pregnancies from 204 women. At pregnancy diagnosis, we observed a majority of chronic ITP cases (71.9 %). At ITP diagnosis, median age of our case-series was 23 years (IQR, 18-31) and median platelet count was 18 x 109/l (IQR, 6-36). Median time from ITP diagnosis to pregnancy was 162 months (IQR, 0-364). Median number of pregnancies prior to ITP diagnosis was 1 (IQR, 0-2) with 1 pregnancy (IQR, 1-2) after ITP diagnosis as a median.
51.6% of women received corticosteroids, immunoglobulins (IVIG) (16.6%), rituximab (7.1%) and/or splenectomy (8.7%) as ITP treatments between or before new pregnancies. On the other hand, 26.5% of women needed treatment for ITP during pregnancy, mainly steroids (13.9%) and IVIG (10.2%).
The median platelet-count nadir during pregnancy was 73 x 109/l (IQR, 31-174). 135 (45.4%) pregnancies had less than 50 x 109 platelets/l with 77 (25.9%) with less than 30 x 109 platelets/l. 57 women (19.2%) exhibited hemorrhagic symptoms, being 30 (10.1%) of them severe bleedings.
Regarding type of delivery, this was vaginal in 187 (62.9%) of pregnancies. Median platelet count at delivery was 111 x 109/l (IQR, 70-187). 47 patients (15.8 %) experienced 60 bleeding episodes. We only observed 52 cases (19.5%) of neonatal thrombocytopenia among 266 living newborns.
Conclusions:
Our results are comparable to previously reported1,2. No severe bleeding complications during pregnancy and/or delivery were observed in our study. Rate of neonatal thrombocytopenia, and therefore, newborn bleeding is low.
No relevant conflicts of interest to declare.
We here describe a primary large B cell non-Hodgkin lymphoma of the right testicle in a 73-year-old male diagnosed with echography and magnetic resonance imaging. Treatment was based upon orchiectomy ...and chemotherapy, without any recurrence 2 years later. Ultrasonography and magnetic resonance findings with normal serum tumoural markers (AFP and B-HCG) can differentiate these tumors from germinal testicular tumors.
