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1.
Blood ; 143(11): 983-995, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-37979133

ABSTRACT

ABSTRACT: Older patients with classical Hodgkin lymphoma (cHL) require more effective and less toxic therapies than younger patients. In this multicenter, prospective, phase 2 study, we investigated a new firstline therapy regimen comprising 6 cycles of prednisone (40 mg/m2, days 1-5), vinblastine (6 mg/m2, day 1), doxorubicin (40 mg/m2, day 1), and bendamustine (120 mg/m2, day 1) (PVAB regimen) every 21 days for patients with newly diagnosed cHL aged ≥61 years with an advanced Ann Arbor stage. A Mini Nutritional Assessment score ≥17 was the cutoff value for patients aged ≥70 years. The primary end point was the complete metabolic response (CMR) rate after 6 cycles. The median age of the 89 included patients was 68 years (range, 61-88 years), with 35 patients (39%) aged ≥70 years. Seventy-eight patients (88%) completed the 6 cycles. The toxicity rate was acceptable, with a 20% rate of related serious adverse events. CMR was achieved by 69 patients (77.5%; 95% confidence interval [CI], 67-86). After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%) from HL (n = 11), toxicity during treatment (n = 4), secondary cancers (n = 6), or other causes (n = 3). The 4-year progression-free survival (PFS) and overall survival rates were 50% and 69%, respectively. Multivariate analysis showed that liver involvement (P = .001), lymphopenia (P = .001), CRP (P = .0005), and comedications (P = .003) were independently associated with PFS. The PVAB regimen yielded a high CMR rate with acceptable toxicity. Over long-term follow-up, survival end points were influenced by unrelated lymphoma events. This trial was registered at www.clinicaltrials.gov as #NCT02414568 and at EudraCT as 2014-001002-17.


Subject(s)
Hodgkin Disease , Humans , Aged , Middle Aged , Aged, 80 and over , Hodgkin Disease/pathology , Vinblastine/adverse effects , Prednisone/adverse effects , Bendamustine Hydrochloride/adverse effects , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Doxorubicin/adverse effects , Cyclophosphamide , Vincristine
5.
Ann Hematol ; 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38443660

ABSTRACT

We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) in France, after a maximum follow-up of five years. Patients were included according to the French marketing authorization in 2016 (i.e. patients with relapsed or refractory CLL or to previously untreated CLL patients with deletion 17p and/or tumor protein p53 mutations unsuitable for chemoimmunotherapy) and could have initiated ibrutinib more than 30 days prior their enrolment in the study (i.e. retrospective patients) or between 30 days before and 14 days after their enrolment (i.e. prospective patients). The results showed that in the effectiveness population (N = 388), the median progression-free survival (PFS) was 53.1 (95% CI: 44.5-60.5) months for retrospective patients and 52.9 (95% CI: 40.3-60.6) months for prospective patients and no difference was shown between the PFS of patients who had at least one dose reduction versus the PFS of patients without dose reduction (p = 0.7971 for retrospective and p = 0.3163 for prospective patients). For both retrospective and prospective patients, the median overall survival was not reached. The most frequent treatment-emergent adverse event of interest was infections (57.6% retrospective; 71.4% prospective). A total of 14.6% of the retrospective patients and 22.4% of the prospective patients had an adverse event leading to death. Our findings on effectiveness were consistent with other studies and the fact that patients with dose reductions had similar PFS than patients without dose reduction is reassuring. No additional safety concerns than those already mentioned in previous studies could be noticed.Trial registration ClinicalTrials.gov, NCT03425591. Registered 1 February 2018 - Retrospectively registered.

6.
Br J Clin Pharmacol ; 87(3): 895-904, 2021 03.
Article in English | MEDLINE | ID: mdl-32559327

ABSTRACT

AIMS: To provide real-life data on patterns of use and safety of ibrutinib. METHODS: A cohort study including all patients initiating ibrutinib between 21 November 2014 and 21 November 2018, and followed for 1 year was conducted. Patient characteristics, ibrutinib use and adverse drug reactions (ADRs) were collected from medical records. Kaplan-Meier analysis estimated the probability of developing ibrutinib-associated serious ADRs (SADRs) with a 95% confidence interval (CI). A Cox proportional hazards model was used to investigate factors associated with SADR occurrence. RESULTS: In total, 102 patients were included in the study. The median age was 70.3 years (interquartile range 64.7-75.6), the male/female gender ratio was 2.9. Almost half the patients (47.1%) were prescribed ibrutinib for chronic lymphocytic leukaemia (CLL). Forty-three patients (42.1%) permanently discontinued ibrutinib in the first year, mostly for progression (51.2%) or ADRs (32.6%). Forty-eight patients (47.1%) experienced at least one ibrutinib-associated SADR. Haematological, infectious and vascular disorders were the most frequent SADRs. The probability of developing ibrutinib-associated SADR was 35.1% (95% CI 26.3-45.7%) at 3 months, 44.8% (35.2%; 55.8%) at 6 months and 54.3% (44.0%; 65.2%) at 12 months. Age ≥80 years (hazard ratio [HR] 2.03; 95% CI 1.02-4.05) and CLL (HR 1.81; 95% CI 1.01-3.25) were significantly associated with a higher risk of SADR occurrence. CONCLUSION: This study found a high cumulative incidence of ibrutinib-associated SADRs within the first year of treatment. In view of the risk of SADR, patients aged ≥80 years or treated for CLL deserve special attention.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Adenine/analogs & derivatives , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Piperidines , Pyrazoles/adverse effects , Pyrimidines/adverse effects
7.
BMC Public Health ; 21(1): 432, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33653294

ABSTRACT

BACKGROUND: Age-adjusted lymphoma incidence rates continue to rise in France since the early 80's, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e. quality of life, long-term sequelae). Epidemiological studies have investigated factors related to lymphoma risk, but few have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour mainly obtained from clinical trials data is partly biased because of patient selection. METHODS: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set up in French areas covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow-up. We aim to include 6000 patients over 4 to 5 years. Adult patients without lymphoma history and newly diagnosed with one of the following 7 lymphoma subtypes (diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, Hodgkin, mature T-cell) are invited to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. Patients are treated according to the standard practice in their center. Clinical data, including treatment received, are extracted from patients' medical records. Patients' risk factors exposures and other epidemiological data are obtained at baseline by filling out a questionnaire during an interview led by a clinical research assistant. Biological samples are collected at baseline and during treatment. A virtual tumor biobank is constituted for baseline tumor samples. Follow-up data, both clinical and epidemiological, are collected every 6 months in the first 3 years and every year thereafter. DISCUSSION: This cohort constitutes an innovative platform for clinical, biological, epidemiological and socio-economic research projects and provides an opportunity to improve knowledge on factors associated to outcome of lymphoma patients in real life. TRIAL REGISTRATION: 2018-A01332-53, ClinicalTrials.gov identifier: NCT03869619 .


Subject(s)
HIV Infections , Lymphoma , Adult , France/epidemiology , Humans , Lymphoma/epidemiology , Lymphoma/therapy , Prognosis , Prospective Studies , Quality of Life
8.
Kidney Int ; 96(1): 94-103, 2019 07.
Article in English | MEDLINE | ID: mdl-30987838

ABSTRACT

The clinicopathological characteristics of kidney infiltration in B-cell lymphoproliferative disorders remain poorly described. We retrospectively studied 52 adults with biopsy-proven malignant B-cell kidney infiltration, including Waldenström's macroglobulinemia (n=21), chronic lymphocytic leukemia (n=11), diffuse large B-cell lymphoma (DLBCL) (n=8), other lymphoma (n=11), and multiple myeloma (n=1). Kidney disease varied according to the underlying lymphoproliferative disorder. In DLBCL, malignant kidney infiltration was prominent, resulting in acute kidney injury (AKI, 75%) and kidney enlargement (88%). In the other types, associated immunoglobulin-related nephropathy (most commonly AL amyloidosis) was more common (45%), and chronic kidney disease with proteinuria was the primary presentation. All patients received chemotherapy. Over a median follow-up of 31 months, 20 patients died and 21 reached end-stage kidney disease. Renal response, achieved in 25 patients (48%), was associated with higher overall survival (97 vs. 37 months in non-renal responders). In univariate analysis, percentage of sclerotic glomeruli, kidney enlargement, and complete hematological response at 6 months were predictive of renal response. In multivariate analysis, concomitant immunoglobulin-related nephropathy was the sole independent predictor of poor renal outcome. In conclusion, clinical presentation of renal lymphomatous infiltration depends on the nature of the underlying lymphoproliferative disorder. In DLBCL, massive renal infiltration manifests with enlarged kidneys and AKI, and the diagnosis primarily relies on lymph node biopsy. In other B-cell lymphoproliferative disorders, the clinicopathological spectrum is more heterogeneous, with a high frequency of immunoglobulin-related nephropathy that may affect renal outcome; thus kidney biopsy is required for early diagnosis and prognostic assessment.


Subject(s)
Acute Kidney Injury/epidemiology , Kidney Cortex/pathology , Lymphoproliferative Disorders/complications , Proteinuria/epidemiology , Renal Insufficiency, Chronic/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Acute Kidney Injury/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Female , Humans , Incidence , Lymphoproliferative Disorders/urine , Male , Middle Aged , Proteinuria/etiology , Proteinuria/pathology , Proteinuria/therapy , Renal Dialysis/statistics & numerical data , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/therapy , Retrospective Studies , Young Adult
9.
Am J Hematol ; 93(6): 729-735, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29473209

ABSTRACT

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m2 /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m2 and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.


Subject(s)
Bendamustine Hydrochloride/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Lymphoma/therapy , Transplantation Conditioning/methods , Acute Kidney Injury/etiology , Adult , Aged , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/adverse effects , Female , Humans , Male , Middle Aged , Prognosis , Risk Assessment , Transplantation, Autologous
10.
Am J Hematol ; 90(11): 1055-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26284823

ABSTRACT

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.


Subject(s)
Antineoplastic Agents/administration & dosage , Immunologic Factors/administration & dosage , Thalidomide/analogs & derivatives , Waldenstrom Macroglobulinemia/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Anemia/chemically induced , Anemia/pathology , Antineoplastic Agents/adverse effects , Drug Administration Schedule , Drug Dosage Calculations , Female , Humans , Immunologic Factors/adverse effects , Lenalidomide , Male , Maximum Tolerated Dose , Middle Aged , Neutropenia/chemically induced , Neutropenia/pathology , Recurrence , Survival Analysis , Thalidomide/administration & dosage , Thalidomide/adverse effects , Treatment Outcome , Waldenstrom Macroglobulinemia/mortality , Waldenstrom Macroglobulinemia/pathology
11.
Cancer ; 120(24): 3952-7, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25116271

ABSTRACT

BACKGROUND: Accurate quantification of immunoglobulin A (IgA) monoclonal immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can impact the assessment of response among patients with multiple myeloma (MM). Therefore, there is a need to identify new assays that better reflect disease burden and response to treatment, and correlate with patient outcome. IgA Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise quantitative measurements of the monoclonal IgA expression and polyclonal-isotype matched suppression. In the current study, the authors assessed the usefulness of these assays in the diagnosis of IgA MM and sought to comment on the prognostic value of the assays. METHODS: A study of 157 patients with IgA MM for whom diagnostic samples were available was performed. HLC measurements were performed on a nephelometer and the results were compared with those of electrophoresis. RESULTS: All presentation sera (100 IgA kappa specimens and 57 IgA lambda specimens) were found to have abnormal IgA HLC ratios (IgA kappa median ratio: 336.2 [range, 8.2-7353] and IgA lambda ratio: 0.011 [range, 0.0003-0.45]). In comparison, SPEP bands were quantifiable in only 105 of 157 samples (67%) (median, 28.5 g/L [range, 2.2 g/L-98 g/L]). Of the total of 157 patients, 12 patients (8%) presented with oligosecretory myeloma (<10 g/L; including 4 patients with nonquantifiable SPEP bands). HLC uniquely allows for the measurement of isotype paired suppression, which was found to be associated with shortened overall survival in the current study. CONCLUSIONS: In the current study, IgA HLC ratios were found to be abnormal in all patients and the assay was able to produce quantifiable results in more MM sera than either SPEP or total IgA, potentially representing a solution to the issue of comigration and oligosecretory MM. These preliminary data require confirmation in larger prospective trials to validate the usefulness of IgA HLC.


Subject(s)
Immunoglobulin A/blood , Immunoglobulin Heavy Chains/blood , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Multiple Myeloma/diagnosis , Multiple Myeloma/therapy , France , Humans , Immunoglobulin A/chemistry , Immunoglobulin Light Chains/blood , Multiple Myeloma/blood , Multiple Myeloma/mortality , Pilot Projects , Predictive Value of Tests , Prognosis , Retrospective Studies
14.
Blood Adv ; 8(6): 1573-1585, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38181767

ABSTRACT

ABSTRACT: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients' quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age >60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre-CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.


Subject(s)
Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Middle Aged , Immunotherapy, Adoptive/adverse effects , Quality of Life , Neoplasm Recurrence, Local , Lymphoma, Large B-Cell, Diffuse/pathology , Biomarkers , Antigens, CD19
15.
Blood Adv ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39163620

ABSTRACT

Tafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 CAR T-cell is currently debated. We analyzed large B-cell lymphoma patients in the DESCAR-T registry treated with axi-cel or tisa-cel in ≥3rd line (L3+) and TAFA-LEN before (n=15, 'TL-pre-CAR-T' set) or directly after (n=52, 'TL-post-CAR-T' set) CAR T-cell. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR-T set. In the TL-post-CAR-T' set, the median follow-up duration (mFUD) was 7 months, and the median progression-free survival, overall survival and duration of response since the 1st treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7 and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell (mPFS2: 5.6 vs. 2 months, p=0.0138; mOS2: not reached vs. 3.8 months, p=0.0034). bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs. 24.9% and 11.6% vs. 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 [2-2.6] vs. 2.4 [1.5-4.2] months, p=0.91; mOS2: 3.3 [1.8-6.4] vs. 5.5 [4.4-6.3] months, p=0.06). In an exploratory analysis of the TL-pre-CAR-T set (mFUD since CAR T-cell: 2.8 months), the median TAFA-LEN treatment duration prior to CAR-T was 3.7 months and no patients were reported to become CD19 negative. The bORR, bCRR, 6-month PFS and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1% and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatments improved outcomes of patients who relapsed after CAR T-cell.

16.
J Hematol Oncol ; 17(1): 61, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107847

ABSTRACT

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.


Subject(s)
Antigens, CD19 , Cytokine Release Syndrome , Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Male , Female , Middle Aged , Antigens, CD19/immunology , Prognosis , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Cytokine Release Syndrome/etiology , Aged , Adult , Neurotoxicity Syndromes/etiology , Biological Products/therapeutic use , Biological Products/adverse effects , France , Aged, 80 and over , Receptors, Antigen, T-Cell
17.
J Clin Oncol ; 42(14): 1612-1618, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38364196

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Depsipeptides , Doxorubicin , Lymphoma, T-Cell, Peripheral , Prednisone , Vincristine , Humans , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Vincristine/administration & dosage , Vincristine/therapeutic use , Prednisone/administration & dosage , Prednisone/therapeutic use , Depsipeptides/administration & dosage , Depsipeptides/therapeutic use , Middle Aged , Male , Female , Aged , Adult , Progression-Free Survival
18.
Blood Adv ; 8(2): 296-308, 2024 01 23.
Article in English | MEDLINE | ID: mdl-37874913

ABSTRACT

ABSTRACT: Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective noninterventional multicentric cohort started in 2018 that included patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on patients with first-line diffuse large B-cell lymphoma (DLBCL) to (1) evaluate the capacity of the cohort to provide robust data through a multistep validation process; (2) assess the consistency of the results; and (3) conduct an exploratory transportability assessment of 2 recent phase 3 CTs (POLARIX and SENIOR). The analysis population comprised 645 patients with DLBCL included before 31 March 2021 who received immunochemotherapy and for whom 3589 queries were generated, resulting in high data completeness (<4% missing data). Median age was 66 years, with mostly advanced-stage disease and high international prognostic index (IPI) score. Treatments were mostly rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP 75%) and reduced dose R-CHOP (13%). Estimated 1-year event-free survival (EFS) and overall survival rates were 77.9% and 90.0%, respectively (median follow-up, 9.9 months). Regarding transportability, when applying the CT's main inclusion criteria (age, performance status, and IPI), outcomes seemed comparable between patients in REALYSA and standard arms of POLARIX (1-year progression-free survival 79.8% vs 79.8%) and SENIOR (1-year EFS, 64.5% vs 60.0%). With its rigorous data validation process, REALYSA provides high-quality RWD, thus constituting a platform for numerous scientific purposes. The REALYSA study was registered at www.clinicaltrials.gov as #NCT03869619.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Large B-Cell, Diffuse , Adult , Humans , Aged , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Rituximab/therapeutic use , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Vincristine/therapeutic use , Doxorubicin/therapeutic use
19.
Cancer ; 119(20): 3680-6, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-23921945

ABSTRACT

BACKGROUND: Lenalidomide in combination with dexamethasone (Len/Dex) is indicated for patients with recurrent/refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long-term exposure to Len/Dex. METHODS: A total of 50 patients with RRMM who were treated with long-term Len for ≥ 2 years from 2 Intergroupe Francophone du Myélome (IFM) centers (Lille and Nancy) were included in the current study. RESULTS: The median age of the patients was 58 years, with 30% of the patients aged >65 years, 49% having an International Staging System stage of 2 and 3, 12% having severe renal insufficiency, and 8% demonstrating an adverse result on fluorescence in situ hybridization. Approximately 56% of the patients received treatment with Len/Dex for ≥ 3 years. The median duration of treatment with Len/Dex was 3 years (range, 2 years-7 years). The response rates for partial response or better and very good partial response or better for the overall cohort were 96% and 74%, respectively, which is similar to patients exposed to Len for ≥ 3 years. With a median follow-up of 4 years, 19 (38%) patients had stopped treatment with Len/Dex. The time to disease progression rate at 37 months was 78% and 91%, respectively, in patients exposed to Len for 2 years to <3 years and for ≥ 3 years (P=025). The safety profile was manageable, similar to that of Len when administered for a shorter period of time; 16% of patients had grade 3 to 4 neutropenia, 6% had thrombopenia, 6% had anemia, and 20% experienced thromboembolic events, all of venous type. The annual incidence rate of second primary malignancy was 1.96% in the current series. CONCLUSIONS: The results of the current study confirmed that the Len/Dex combination is feasible for long-term use in patients with RRMM, with a significant benefit noted in terms of time to disease progression for prolonged treatment with Len/Dex.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Adult , Aged , Dexamethasone/administration & dosage , Disease Progression , Female , Follow-Up Studies , Humans , Lenalidomide , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Thalidomide/administration & dosage , Thalidomide/analogs & derivatives
20.
Blood Adv ; 7(15): 3978-3983, 2023 08 08.
Article in English | MEDLINE | ID: mdl-36129842

ABSTRACT

Preservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility.


Subject(s)
Hodgkin Disease , Pregnancy , Child , Infant, Newborn , Humans , Female , Adolescent , Young Adult , Adult , Hodgkin Disease/complications , Hodgkin Disease/drug therapy , Vinblastine/adverse effects , Bleomycin/adverse effects , Dacarbazine/adverse effects , Doxorubicin/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fertility
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