scholarly journals Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines

2021 ◽  
Vol 5 (5) ◽  
pp. 1483-1489
Author(s):  
Alden A. Moccia ◽  
Kimberly Schaff ◽  
Ciara Freeman ◽  
Paul J. Hoskins ◽  
Richard J. Klasa ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Standard Dose ◽  
Clinical Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Curative Intent ◽  
International Prognostic Index Score ◽  
The Impact

Abstract Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 2:1 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.

Impact of time from diagnosis to initiation of curative chemotherapy on survival of patients with diffuse large B-cell lymphoma (DLBCL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8552-8552
Author(s):  
Kevin A. Hay ◽  
Benny Lee ◽  
Ozge Goktepe ◽  
Joseph M. Connors ◽  
Laurie Helen Sehn ◽  
...  
Keyword(s):  
Demographic Data ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Geographic Region ◽  
Time Interval ◽  
Curative Intent ◽  
Significant Difference ◽  
The Impact

8552 Background: DLBCL is potentially curable with combination chemotherapy such as CHOP-R. Although it is generally regarded appropriate to start chemotherapy promptly after diagnosis, the impact of the time from diagnosis to treatment initiation on treatment outcome is unknown. Methods: Patients diagnosed with DLBCL and treated with at least one cycle of CHOP-R with curative intent during 2003 – 2008 in British Columbia were identified in the Lymphoid Cancer Database. Additional demographic data were obtained from the BC Cancer Registry. The BC Cancer Agency provincial pharmacy database was used to obtain dates of chemotherapy administration. The impact of the time interval from the date of pathologic diagnosis to treatment on overall survival (OS) and progression-free survival (PFS) was evaluated. Results: A total of 793 patients were identified: 199 (25%) received CHOP-R <2 weeks after diagnosis, 244 (31%) at 2-4 weeks, 293 (37%) at 5-8 weeks, and 57 (7%) at >8 weeks. High international prognostic index, primary mediastinal DLBCL, and hospitalization at the time of CHOP-R start were associated with earlier initiation of chemotherapy (p<0.001 for all factors). Distance to chemotherapy from home (p=0.237), rural vs. urban location (p=0.952), geographic region (p=0.458), and median household income (p=0.127) were not associated to treatment start. Five-year PFS and OS respectively were 54% (SD 4%) and 61% (SD 4%) for treatment <2 weeks, 63% (SD 3%) and 66% (SD 3%) for 2-4 weeks, 70% (SD 3%) and 74% (SD 3%) for 5-8 weeks, and 60% (SD 7%) and for 61% (SD 8%) >8 weeks, p=0.006 (PFS) and p=0.024 (OS). A multivariate analysis demonstrated no significant difference between the groups. Conclusions: In a publicly funded healthcare system, earlier initiation of chemotherapy was strongly associated with poor prognostic factors, as well as inferior PFS and OS. The timing of chemotherapy initiation appears to be related to clinical factors instead of system or socioeconomic barriers. Notwithstanding the lack of detrimental outcomes in those commencing CHOP-R after 8 weeks, clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.

scholarly journals Cepp in Previously Untreated Patients with Mature T Cell Lymphomas

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1371-1371
Author(s):  
Hian Li Esther Chan ◽  
Joanne Lee ◽  
Sanjay De Mel ◽  
Anand Devaprasath D. Jeyasekharan ◽  
Yen Lin Chee ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Clinical Stage ◽  
International Prognostic Index ◽  
Autologous Transplantation ◽  
Prognostic Index ◽  
Disease Stage ◽  
Control Group ◽  
Curative Intent ◽  
Salvage Regimen

Abstract Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

scholarly journals A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515

Blood ◽  
2012 ◽  
Vol 120 (6) ◽  
pp. 1210-1217 ◽  
Author(s):  
Alison T. Stopeck ◽  
Joseph M. Unger ◽  
Lisa M. Rimsza ◽  
Michael LeBlanc ◽  
Brent Farnsworth ◽  
...  
Keyword(s):  
B Cell ◽  
Standard Dose ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Trial ◽  
Large B Cell

Abstract S0515 was a phase 2 trial to determine whether the addition of bevacizumab to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab (R-CHOP) would improve progression-free survival (PFS) without adding significant toxicity in patients with newly diagnosed advanced diffuse large B-cell lymphoma. A total of 73 patients were enrolled. For the 64 eligible patients, median age was 68 years, and 60% had International Prognostic Index scores more than or equal to 3. The observed 1- and 2-year PFS estimates were 77% and 69%, respectively. These PFS estimates were not statistically different from the expected PFS for this population if treated with R-CHOP alone. Grade 3 or higher toxicities were observed in 81% of patients, including 2 grade 5 events. The majority of serious toxicities were hematologic but also included 5 patients with gastrointestinal perforations, 4 patients with thrombotic events, and 11 patients who developed grade 2 or 3 left ventricular dysfunction. Higher baseline urine VEGF and plasma VCAM levels correlated with worse PFS and overall survival. In conclusion, the addition of bevacizumab to R-CHOP chemotherapy was not promising in terms of PFS and resulted in increased serious toxicities, especially cardiac and gastrointestinal perforations. This study is registered at www.clinicaltrials.gov as #NCT00121199.

Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma

2017 ◽  
Vol 35 (31) ◽  
pp. 3538-3546 ◽  
Author(s):  
John P. Leonard ◽  
Kathryn S. Kolibaba ◽  
James A. Reeves ◽  
Anil Tulpule ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
The Impact ◽  
Large B Cell

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

No Benefit from Rituximab Containing Regimens in Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3615-3615
Author(s):  
Gonzalo Gutiérrez-García ◽  
Luis Colomo ◽  
Neus Villamor ◽  
Leonor Arenillas ◽  
Antonio Martínez ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Primary Cns Lymphoma ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous category of lymphoid tumors that comprises different clinical forms not fully recognized in the WHO classification. In this regard, extranodal (EN) DLBCLs have particular clinicobiological features and outcome, sometimes related to the specific site where the lymphoma arises. Nowadays, rituximab plus chemotherapy (CT) is the gold-standard in the treatment of DLBCL. However, the superiority of rituximab-CT (R-CT) over CT alone has not been addressed for all the clinical subsets of the disease and, in fact, the clinical role of the new therapies might be different for primary nodal or EN DLBCLs. The aim of this study was to assess the impact of rituximab in patients suffering from nodal or EN DLBCL. Two-hundred and thirty non-immunocompromised patients (112M/118F; median age, 61 years) diagnosed with CD20+DLBCL in a single institution between 1997 and 2006 (five years before and after establishing R-CT as the standard treatment in DLBCL) and treated with adriamycin-containing regimens were the subject of the present study. The series included 148 primary nodal and 82 EN DLBCL. Patients with primary CNS lymphoma were excluded and lymphomas arising at Waldeyer ring were considered as nodal DLBCL. The main EN sites were GI (n=26), bone (n=13), soft tissue (n=13), lung/pleura (n=9), liver (n=9), and other (n=12). Main clinico-biological and evolutive variables were analyzed. One hundred nineteen patients received only CT and 111 R-CT. Eighty-seven cases with available information were assigned to germinal center B-cell-like (GCB) (41%) or non-GCB (59%) groups according to the Hans method (Blood2004;103:275–82) based on CD10, BCL6 and MUM1 expression. Main initial features, including the primary nodal or EN origin, international prognostic index (IPI), and GCB/non-GCB categories were similar for CT and R-CT groups. No correlation was observed between the GCB/non-GCB groups and the primary site of the tumor, although nodal lymphomas more frequently expressed MUM1 than EN (69% vs. 31%, respectively; p=0.01). CR rate and 5-year overall survival (OS) according to the treatment arm (CT vs. R-CT) is detailed for the whole series and for the nodal and EN groups in the table and OS curves depicted in the figure. In the whole series, variables predicting poor OS in the multivariate analysis were high-risk IPI (RR 2.5; p<0.001), primary nodal involvement (RR 1.6; p=0.04) and no R-CT treatment (RR 1.9; p=0.002). In the nodal group, IPI and no R-CT maintained the prognostic value, whereas in the primary EN only IPI predicted OS. Moreover, no difference in OS was observed according to the nodal or EN origin in those patients receiving R-CT. Biological subtypes GCB vs. non-GCB did not add predictive information neither in the whole series nor in the nodal or EN groups. In conclusion, patients with primary EN DLBCL seem to have little benefit from the use of R-CT. Nevertheless, this intriguing observation should be confirmed in further prospective studies. Complete response CR (%) 5-years OS (%) CT R-CT CT R-CT *p<0.002 R-CT vs. CT All cases (n=230) 59 79* 46 70* Primary nodal (n=148) 54 78* 34 71* Primary extranodal (n=82) 68 78 70 69 Figure Figure

Type of tissue biopsy and outcomes in diffuse large B-cell lymphoma (DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13569-e13569
Author(s):  
Sanjal Desai ◽  
Raphael Mwangi ◽  
Rebecca L. King ◽  
Matthew J. Maurer ◽  
James Robert Cerhan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Initial Diagnosis ◽  
Molecular Testing ◽  
Tissue Biopsy ◽  
The Impact ◽  
Biopsy Method

e13569 Background: Progress in understanding the molecular biology of DLBCL has led to development of complex molecular classifications that rely on sequencing methods. These molecular clusters are defined by activation of distinct pathways and may aid in selecting targeted therapy. In the molecular era, tissue requirements in clinical trials have increased to ensure sufficient tissue for molecular testing, potentially resulting in bias for enrollment of patients with larger excisional biopsies (EB). We examined the impact of tissue biopsy method on outcomes of DLBCL in a prospective observational study. Methods: Consecutive adult patients with DLBCL within 9 months from their initial diagnosis were enrolled into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). Demographics, clinical variables, type of tissue biopsy (EB vs. core needle biopsy (CNB)) for initial diagnosis and initial treatment were recorded at baseline. Pts were contacted every 6 months from the date of diagnosis for first 3 years and then annually thereafter. Study objectives were event free survival (EFS) and overall survival (OS) by tissue biopsy method. Results: A total of 1061 patients with newly diagnosed DLBCL, from 2002 to 2015, were included. The table lists baseline characteristics of the cohort. 593 (56%) pts underwent EB and 468 (44%) underwent CNB for initial diagnosis. A significantly higher proportion of patients receiving CNB had performance status >=2, advanced stage, high risk disease by international prognostic index (IPI), abnormal lactate dehydrogenase. Median time from diagnosis to treatment initiation (DTI) was significantly shorter in the CNB group (13 days) than EB group (19 days). 2-year EFS (60% vs 75%, HR 0.75 (0.6-0.9), p <0.01) was significantly lower in CNB than EB group. There was a trend towards lower OS (75% vs 80%, HR: 0.8 (0.6-0.95), p =0.049) in CNB than EB group. Conclusions: Patients undergoing CNB are more likely to have higher risk disease, shorter DTI and survival compared to those undergoing EB. A need for large amount of diagnostic tissue in biomarker driven clinical trials may result in disproportional exclusion of high risk DLBCL pts who have inferior outcomes after standard treatment and could potentially benefit from novel agents, resulting in overperformance of the control arm. The need for tissue must be carefully balanced against resulting selection bias.[Table: see text]

scholarly journals Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival

Blood ◽  
2009 ◽  
Vol 114 (11) ◽  
pp. 2273-2279 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Kerry J. Savage ◽  
Olga Ludkovski ◽  
Susana Ben-Neriah ◽  
Ryan Woods ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
International Prognostic Index Score ◽  
Risk Patients ◽  
Bcl2 Protein

Abstract BCL2 and MYC are oncogenes commonly deregulated in lymphomas. Concurrent BCL2 and MYC translocations (BCL2+/MYC+) were identified in 54 samples by karyotype and/or fluorescence in situ hybridization with the aim of correlating clinical and cytogenetic characteristics to overall survival. BCL2+/MYC+ lymphomas were diagnosed as B-cell lymphoma unclassifiable (BCLU; n = 36) with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL); DLBCL (n = 17), or follicular lymphoma (n = 1). Despite the presence of a t(14;18), 5 cases were BCL2 protein–negative. Nonimmunoglobulin gene/MYC (non-IG/MYC) translocations occurred in 24 of 54 cases (44%) and were highly associated with DLBCL morphology (P < .001). Over a median follow-up of 5.3 years, 6 patients remained in remission and 32 died within 6 months of the MYC+ rearrangement, irrespective of whether MYC+ occurred at diagnosis (31 of 54) or transformation (23 of 54; P = .53). A non-IG/MYC translocation partner, absent BCL2 protein expression and treatment with rituximab-based chemotherapy, were associated with a more favorable outcome, but a low International Prognostic Index score and DLBCL morphology were independent predictors of overall survival. A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive lymphomas may identify a group of high-risk patients who may benefit from chemotherapeutic regimens that include rituximab and/or BCL2-targeted therapy.

scholarly journals PRIMARY BONE LYMPHOMAS: RETROSPECTIVE ANALYSIS OF 42 CONSECUTIVE CASES

2018 ◽  
Vol 26 (2) ◽  
pp. 103-107
Author(s):  
TELMA MURIAS DOS SANTOS ◽  
JUAN PABLO ZUMÁRRAGA ◽  
FÁBIO MAZETTI REAES ◽  
CARLOS HENRIQUE MAÇANEIRO JUNIOR ◽  
ANDRÉ MATHIAS BAPTISTA ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
International Prognostic Index ◽  
Case Series ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Level Of Evidence ◽  
International Prognostic Index Score ◽  
Primary Bone

ABSTRACT Objective: It is difficult to define parameters for management and factors associated with primary bone lymphoma (PBL). This article presents the experience in a single institution with 42 patients with PBL over a 16-year period (2000-2016). Methods: Fifty-five patients were retrospectively evaluated, and forty-two were included (76.3%). Results: Median age at diagnosis was 51.5 years, and median follow-up was 102.7 months. One patient had HIV. Pain in the affected site was the most prevalent symptom. The average time between symptom onset and diagnosis was 5.4 months. The vertebrae were most affected (n=16, 33.3%). According to the International Prognostic Index Score (IPI), 64.3% of the patients were classified as having low-grade lymphoma and 25.7% as low-intermediate. The most common histology was diffuse large B cell lymphoma (DLBCL) (85.7%). Immunophenotyping was CD20 positive in 93.5% of patients, and 11 patients had pathological fracture. All patients received chemotherapy and 30% of the regimens included rituximab. Thirty-eight percent of patients received radiation therapy. Overall survival was 50%, and survival median time was 80 months. Age and chemotherapy regimen influenced patient survival. Younger patients and patients who received RCHOP had better prognoses. Conclusions: The choice of chemotherapy regimen associated with age influenced survival for patients with PBL. Level of Evidence IV; Case series.

Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7512-7512
Author(s):  
Catherine S. Magid Diefenbach ◽  
Pau Abrisqueta ◽  
Eva Gonzalez-Barca ◽  
Carlos Panizo ◽  
Jose Maria Arguinano Perez ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Unmet Need ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Primary Analysis ◽  
Phase 1B ◽  
The Impact ◽  
Cutoff Date

7512 Background: The combination of Pola-R-Len may enhance anti-tumor response in R/R DLBCL. We report the primary analysis of the R/R DLBCL cohort in a Phase 1b/2 study (GO29834; NCT02600897). Methods: Pts received induction with 6 x 28-Day (D) cycles (C) of: Pola 1.8mg/kg intravenous (IV; C1−6: D1); R 375mg/m2 IV (C1−6: D1) and oral Len 10–20mg (dose escalation) or recommended Phase 2 dose (RP2D) daily on D1–21. Pts with a response at end of induction (EOI) received 6 months (mo) consolidation with R 375mg/m2 (D1 every 2 mo) and Len 10mg (D1–21 monthly). Primary endpoints were safety/tolerability and positron emission tomography (PET)-complete response (CR) rate at EOI by independent review committee (IRC) by modified Lugano criteria. Results: At primary analysis (Sep 08, 2020), 57 pts were enrolled. Median age was 71 years (range 28–92); male (67%); Ann Arbor Stage III–IV (86%); International Prognostic Index 3–5 (60%); median 2 prior therapies; prior bone marrow transplant (11%); prior CAR-T therapy (5%); primary refractory (49%) and refractory to last therapy (65%). Grade 3–4 adverse events (AEs) were experienced by 75% of pts, most commonly, neutropenia (58%), thrombocytopenia (14%), infections (14%) and anemia (11%). AEs led to Len dose reduction in 25% and interruption in 63% of pts. One Grade 5 treatment-related AE (neutropenic sepsis) was reported. In total, 49 pts were treated at RP2D (Pola 1.8mg/kg + Len 20mg). IRC PET-CR rate at EOI was 29% (Table). A best overall response (BOR) assessed by investigator (INV) was seen in 36/49 (74%) pts with 17/49 (35%) pts achieving a CR; of these, 14/17 (82%) remain in remission at the cutoff date. Median duration of response (DOR) was 8.1 mo (95% confidence interval [CI]: 4.7–not evaluable [NE]). After a median follow-up of 9.7 mo, median progression-free survival (PFS) and overall survival (OS) were 6.3 mo (95% CI: 4.5–9.7) and 10.9 mo (95% CI: 7.4–NE), respectively. Conclusions: Our study of the novel triplet combination, Pola-R-Len, demonstrates a tolerable safety profile. This first efficacy report of Pola-R-Len shows promising activity in a difficult-to-treat R/R DLBCL population, particularly in pts achieving CR, a large proportion of whom remain in remission at the cutoff date. Further evaluation of Pola-R-Len and the impact of consolidation therapy is warranted to address the significant unmet need in this patient population. Clinical trial information: NCT02600897. [Table: see text]

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