scholarly journals Pediatric Hodgkin’s Lymphoma: 5-Year Experience at Single Center in Pakistan

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5455-5455
Author(s):  
Shazia Riaz ◽  
Safia Khan ◽  
Farhana Badar
Keyword(s):  
Conflicts Of Interest ◽  
Complete Response ◽  
Developed Countries ◽  
Single Center ◽  
Bulky Disease ◽  
Excellent Outcome ◽  
Pediatric Hodgkin Lymphoma ◽  
End Of Treatment ◽  
Night Sweats ◽  
Pediatric Hodgkin’S Lymphoma

Abstract OBJECTIVES: To review patients’ characteristics and treatment outcome pattern of pediatric hodgkinlympoma in a well funded center in developing country MATERIALS & METHOD: This was retrospective review of data of 301 pediatric hodgkin lymphoma patients up to 18 years of age treated in Shaukat Khanum Memeorial Cancer Hospital & Research Center, Lahore, Pakistan, during 2009 to 2013. RESULTS: Total No. of patients was 301, 81% were male. The median age of studied data was 9 years; ranging from 2 to 18 years. B symptoms in the form of fever, weight loss and night sweats were found in 51%, 29% and 34%, respectively. Median stage was 3 with neck bulky disease in 28% and Medistinal widening in 18% of patients. Trend of histopathology was mixed cellualrity at 56.5%. Most common treatment regime was ChlVPP/ABVD (59.5%); 30.6% of these 301 patient also got radiotherapy. At the end of treatment complete response was reported in 76.5%; 11.3% of these were relapsed afterward. CONCLUSION: Our data shows excellent outcome of pediatric hodgkin lympoma and results are comparable to that of developed countries. Disclosures No relevant conflicts of interest to declare.

Long-Term Remission (>3 years) after Rituximab Monotherapy Used for Patients with Relapsed Indolent Non-Hodgkin Lymphomas (NHL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1709-1709
Author(s):  
Anne-Sophie Michallet ◽  
Florence Beckerich ◽  
Fadhela Bouafia-Sauvy ◽  
Daniel Espinouse ◽  
Gilles Salles ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Complete Response ◽  
Bulky Disease ◽  
Entire Cohort ◽  
The Subject ◽  
Disseminated Disease ◽  
Question Today ◽  
Term Response

Abstract Background: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has dramatically changed the treatment and outcome of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in a large majority of patients. Aim: The objective of this retrospective study is to evaluate the long-term efficacy of rituximab monotherapy (4 weekly infusion at induction followed by 4 infusion every 2 months as consolidation) used for patients with relapsed indolent NHL. Results: From May 1998 through January 2011, Among 919 patients with indolent NHL treated in our department, 488 (53%) relapsed and were treated with rituximab alone (first and later relapse). 126 (26%) responded and were still in response 2 years later. These 126 patients (68 (54%) males and 58 (46%) females with a median age of 61 y; range: 17-94) are the subject of our analysis. 24% were over 70 years old, 45% were in first relapsed and 25% in later relapsed. Only 16% of the population have more than one co-morbidities (cardiac and or renal respectively); 79% a normal PS (0-1) with only 4 patients having a PS >2; 80% no bulky disease but 72% a disseminated disease (73% stage III and IV). In this study, 60 (48%) patients had a follicular lymphoma with 50% at an intermediate risk group according to the FLIPI score ; 20 (16%) a marginal zone lymphoma, and 43 (34%) a small lymphocytic or lymphoplasmacytic lymphoma and 3 patients other characteristics of lymphoproliferative disorders. After rituximab monotherapy, 55% of the entire cohort was in complete response (CR) and 31% in CRu or partial response and 5% in stable disease. Among these 126 patients, 74% progressed later than 3 years (38% later than 5 years). With a median follow-up of 6.5 years, 4-year and 8-year PFS were 70% and 30%, respectively. 18% had transformation into Richter syndrome and 12 patients have died. Conclusion: Rituximab monotherapy is an effective therapy in selected relapsed indolent NHL and allows long-term response. This strategy could be used as “spare of chemotherapy” which is an important question today, especially in indolent not curable disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hodgkin's Lymphoma Outcome: A Retrospective Study from Three Tertiary Centers in Saudi Arabia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5059-5059
Author(s):  
Ruaa Shafi ◽  
Mubarak M Al-Mansour ◽  
Solaf Sami Kanfar ◽  
Hani Hassan Al Hashmi ◽  
Ahmad S. Alsaeed ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Developed Countries ◽  
Initial Therapy ◽  
Disease Stage ◽  
Term Outcome ◽  
Bulky Disease ◽  
Long Term Outcome

Abstract Background: Hodgkin lymphoma (HL) demonstrates considerable clinicopathologic variations in different parts of the world. Prompted by the limited availability of data particularly the long-term outcome of HL in developing countries, we carried out this retrospective data analyses. Methods: A retrospective review of eligible adult HL patients managed at three tertiary centers in Saudi Arabia between January 1997 to December 2012. Results: The review included 340 patients with median age of 26 years (range15-82). 53% of patients were male, 74% had an advanced stage, 19% had bulky disease, and 70% had low to intermediate risk according to Hasenclever index. Nodular sclerosis was the most common histological subtype (59%). ABVD was given to 92% and radiotherapy to 43%. Response to initial therapy was complete, partial, and disease progression was reported in 91%, 5%, and 2 % of patients, respectively. At a median follow-up of 50 months, the actuarial freedom from treatment-failure at 5-year was 74%, and with an overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently projected an adverse outcome. Conclusion: This study confirms that our patients population demonstrated a comparable outcome to that reported from developed countries. Disclosures No relevant conflicts of interest to declare.

Interim and End-of-Treatment 18F-FDG-PET Evaluation of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 6 Cycles of Dose-Dense R-CHOP-14 Immunochemotherapy Plus Pegfilgrastim for First-Line Treatment: An Open-Label Clinical Trial in Spain.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3692-3692 ◽  
Author(s):  
Eva Gonzalez-Barca ◽  
Miguel Canales ◽  
Antonio Salar ◽  
Albert Oriol ◽  
María Jesús Vidal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Interim Pet ◽  
Radiology Reports ◽  
End Of Treatment ◽  
Response To Chemotherapy ◽  
Dose Dense

Abstract Abstract 3692 Poster Board III-628 Background DLBCL is the most frequent aggressive non Hodgkin's lymphoma in adults. The International Prognostic Index (IPI) is currently the most used tool to identify different risk patients. The role of an interim PET to early identify patients with bad response to chemotherapy is controversial. However end of therapy PET correlates strongly with progression free survival. Aims The aim of this analysis is to evaluate the results of an interim PET (after 2 chemotherapy cycles) and PET at the end of treatment (6 chemotherapy cycles of dose-dense R-CHOP) in patients with DLBCL. Methods This is a prospective clinical trial for patients with DLBCL older than 65 with IPI 0-5 or younger than 65 with IPI 0-2. Treatment consists of 6 cycles of R-CHOP administered every 14 days followed by pegfilgrastim (6 mg per cycle) on day 2. 63 patients, who completed all 6 cycles of chemotherapy and have had both PET evaluations after 2 cycles of R-CHOP and at the end of treatment, have been selected for this sub-analysis. All evaluations were made by combined PET/ CT, except for 14 patients who were evaluated by PET alone. PET was determined to be positive or negative based on the radiology reports. Interim PET results did not change the planned treatment. Results 109 patients were analyzed for response. 17 patients (15.5%) did not finish 6 cycles of treatment: 2 due to serious adverse events, 3 due to progression disease / stabilization, 5 due to investigators decision and 7 due to death. Over 92 patients who completed 6 cycles of treatment, 63 patients who had both a PET evaluation after 2 cycles of treatment and at the end of treatment, were included in this analysis. Median age was 60 years old (range 18.2-78.9), 30 (47.6%) were older than 65, 32 (51%) were male. Fifty-four (85.7%) had ECOG 0-1. Characteristics of the disease at diagnosis were as follows: stage III-IV: 39 (61.9%), bulky disease: 15 (23.8%), > 2 extra-nodal sites involvement: 4 (6.4%), B symptoms: 15 (23.8%), elevated LDH: 31 (49.2%), elevated beta-2-microglobulin: 20/57 (35.1%), IPI 3-5: 19 (30.2%). Thirty-one (49.2%) patients achieved a negative PET evaluation after 2 R-CHOP cycles and 53 (84.1%) at the end of treatment. Twenty-nine (93.6%) patients with an interim negative PET remained negative at the end of therapy. Among the 32 patients with a positive PET after 2 cycles of therapy, 24 (75%) turned negative at the end of therapy. Patients with bulky disease had a positive interim PET more frequently (66.7% vs 45.8%), but most of them turned negative at the end of treatment (positive PET 6.7%). Conclusions An early positive PET is not predictive of a persistent positivity at the end of treatment. In fact, patients with bulky disease more frequently have an early positive PET, but most of them turn negative after 6 cycles of R-CHOP14. On the other hand, an early negative PET is highly predictive of a negative end-of-treatment PET. In conclusion, our data do not support an early intensification of patients with DLBCL with a positive interim PET, although a longer follow-up is necessary to confirm these results. Disclosures: No relevant conflicts of interest to declare.

Related or Unrelated Donor Results in Similar Outcomes after Hsct; Single Center Experience in Colombia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5512-5512
Author(s):  
Virginia Abello ◽  
Carmen Rosales ◽  
Manuel Rosales ◽  
Javier Figueroa ◽  
Iris Cordoba ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Developed Countries ◽  
Rank Test ◽  
Time Interval ◽  
Unrelated Donor ◽  
Fisher Exact Test ◽  
Late Time ◽  
Single Center

Abstract INTRODUCTION ASTC is the standard treatment in multiple hematologic diseases; unfortunately most patients do not have a compatible family donor, URD ASCT is an alternative to those patients. There is evidence from developed countries that outcomes may be similar regardless the donor, but there is not enough information from Latin America regarding survival after URD ASCT. We compared survival at 1 and 3 years from patients transplanted using related or unrelated donors in a single center in Colombia. MATERIALS AND METHODS Paired analysis was performed comparing one URD ASCT with one or two RD ASCT with similar characteristic in terms of age, diagnosis (AML, ALL, aplasia, CML, MDS), EBMT risk, year of transplant and conditioning regimen. Chi-square or Fisher exact test was used to compare the groups (p<0.05). The survival curves of Kaplan-Meier and log-rank test (p<0.05) were used to estimate the probabilities of one (OS1) and three (OS3) overall survival in different groups according to EMBT score risk. RESULTS 28 URD ASCT were performed between 2011 and 2014, 24 of those (18 matched and 6 missmatched URD ASCT) were paired with 41 RD ASCT. Of those 62% were males, mean age was 33.4 years, 70.8% patients were in early stages, almost 60% had more than 12 months interval between diagnosis and transplant. Most common diagnoses were acute lymphoid leukemia and acute myeloid leukemia. 80% of donors where found through NMDP. No significant differences in sex, age, disease status (early, intermediate, late), time interval from diagnosis to transplantation, and patient-donor sex combination, ranked according to EBMT risk score, were find between the tow groups. Median follow-up was 322 days (range 165-693), for the whole group. There were no significant differences in the OS1 or OS3 between URD o RD ASCT, in different EBMT score groups. Low risk: OS1: URD 86.6% vs RD 75.8%, p = 0.46; OS3: 86.6% vs 68.9%, p = 0.28. High risk OS1 75% vs 63.6%, p=0.92; OS3 75% vs 63.6%, p=0.92. CONCLUSIONS In this cohort of patients, the type of donor had no influence in the outcome measured in terms of OS. This is the first experience with URD ASCT in Colombia; longer follow up of this cohort is needed to confirm this results, but our findings suggest this transplantation modality is a real alternative to patients in our country in need of a transplant without an HLA identical related donor. Disclosures No relevant conflicts of interest to declare.

scholarly journals Predictors of Poor Response to Salvage Chemotherapy in Relapsed/ Refractory Pediatric Hodgkin Lymphoma- A Retrospective Analysis from Tertiary Cancer Centre in India

2018 ◽  
Vol 54 (03) ◽  
pp. 160-170
Author(s):  
Sainath Bhethanabhotla ◽  
Sreenivas Vishnubhatla ◽  
Sameer Bakhshi
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Hodgkin Lymphoma ◽  
Poor Response ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Pediatric Hodgkin Lymphoma ◽  
Stage 4

ABSTRACT Background: Previous studies identified prognostic factors for survival in relapsed pediatric Hodgkin lymphoma (HL) who received salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, data regarding predictors of poor response to salvage chemotherapy is limited. Methods: We conducted retrospective study in all relapsed HL treated from January 2003 to December 2013. Logistic regression analysis was done to identify predictors of response to salvage chemotherapy. Cox regression analysis was done to identify prognostic factors for Freedom from treatment failure (FFTF) and overall survival (OS). Results: Forty six patients had relapsed HL. Among 45 patients who received salvage chemotherapy only 34 (73.4%) underwent ASCT. Stage 4 disease (p=0.02) and bulky disease at relapse (p=0.03) were predictors of poor response to salvage chemotherapy. FFTF and OS at 5 yr for entire cohort were 50.1% and 63.3%, respectively, while the same for patients who underwent ASCT were 66.3% and 80.7%, respectively. Among ASCT patients, those who had primary refractory /early relapse [HR-4.7, (95% CI-1, 22); p=0.05] had significant impact on 5 yr FFTF whereas disease status at transplant (CR vs. No CR) had significant impact on 5 yr OS [HR-4.6, (95% CI-1.03, 20.5); p=0.04]. Conclusions: Identification of predictors of poor response to salvage chemotherapy is an unmet need in the management of pediatric HL since complete response (CR) before transplant is independent predictor of survival. Stage 4 and bulky disease at relapse are high risk factors to predict incomplete response. Future trials should explore newer agents for effective salvage for these patients to attain complete response before ASCT.

Chlorambucil PLUS Rituximab As FRONT-LINE THERAPY in Elderly or Unfit Patients Affected by B-CELL Chronic Lymphocytic Leukemia: Results of A Single-Centre Retrospective Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4604-4604
Author(s):  
Luca Laurenti ◽  
Barbara Vannata ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
Francesco Santini ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Fish Analysis ◽  
Median Dose ◽  
Bulky Disease ◽  
Overall Response ◽  
Line Therapy ◽  
Trisomy 12 ◽  
Unfit Patients

Abstract Abstract 4604 Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl). However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 23 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg monthly for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). Fifteen patients were male and 8 were female, with a median age at the time of treatment of 70 years (range 58 to 81 years). Eight patients (35%) were unfit with a median age of 68 years (range 58 to 79 years). Five patients were in stage A/I, 10 were in stage B/II and 8 in stage C/IV. FISH analysis was done in all patients: 78% showed karyotype abnormalities. Low-risk FISH karyotype was detected in 20/23 pts: 12 of them had del(13q14), 1 had trisomy 12, 1 trisomy 12 and del(13q14) and 6 had a normal karyotype. Three patients showed a high risk karyotype: all of them had del(11q). None of the patients had a 17p deletion. Nineteen pts were studied for IGHV mutational status (83%), 12 had unmutated while 7 had mutated IGHV genes. Twenty-one patients were evaluable for response to treatment. The median number of Chl and RTX cycles administered in the 21 patients who completed the treatment protocol was 8 (range 6 to 8 cycles) and 6 (range 4 to 6 cycles) respectively. The median total dose of Chl administered during the treatment was 600 mg per patient (median dose 85 mg each cycle). The median dose of RTX administered was 4000 mg per patient (median dose 710 mg each cycle). Among 21 pts evaluable for response, the Overall Response Rate (ORR) was 76%. Six pts (28%) obtained a complete response, 10 pts (48%) obtained a partial response. No significant statistical differences were noticed in terms of ORR for age more or less than 70 years, fitness status, bulky disease, cytogenetic risk abnormalities or IgVH, ZAP-70 and CD38 categories. On an intention to treat basis the median PFS was not reached at a median time of 21 months (range 2–45). Eleven pts experienced progression after treatment at a median time of 20 months (range 2–36). No significant statistical differences were found among the analyzed risk groups. After a median time of 25 months (range, 2–45 months), TTR was not reached. No significant statistical differences were noticed between the Unmutated and Mutated IgVH groups and for ZAP-70 and CD38 categories with respect to TTR. At present the median follow-up is 29 months, with an OS rate of 80% (19/23). None of the risk factors analyzed were found to influence significantly the OS. In conclusion, this study suggests that the combination Chl-R is a safe and effective therapeutic option for untreated B-CLL pts that are not eligible for fludarabine treatment because of age and/or comorbidities. A multicentre trial to confirm these data is planned. Disclosures: No relevant conflicts of interest to declare.

Metastatic pancreatic cancer with complete response to FOLFIRINOX treatment

2021 ◽  
Vol 14 (5) ◽  
pp. e238395
Author(s):  
Paige T Shelemey ◽  
Carla P Amaro ◽  
Danny Ng ◽  
Vincent Falck ◽  
Vincent C Tam
Keyword(s):  
Pancreatic Cancer ◽  
Complete Response ◽  
Large Mass ◽  
Scar Tissue ◽  
Pancreatic Mass ◽  
Metastatic Pancreatic Cancer ◽  
Liver Lesions ◽  
Ultrasound Guided ◽  
Cancer Antigen ◽  
Night Sweats

A 59-year-old woman presented with abdominal pain associated with nausea and night sweats. A large mass was found in the pancreatic tail and innumerable liver lesions were identified. Ultrasound-guided biopsy of a liver nodule confirmed moderately differentiated adenocarcinoma consistent with a pancreatobiliary primary. On FOLFIRINOX chemotherapy, subsequent CT scans showed shrinkage of the pancreatic mass and liver metastases. Her cancer antigen 19-9 (CA 19-9) normalised after 11 months. Oxaliplatin was discontinued due to peripheral neuropathy but she completed 37 cycles of FOLFIRI during which her pancreatic mass disappeared, liver lesions decreased in size and were subsequently deemed to be scar tissue by the radiologist. After 4 years of treatment, the patient agreed to a break from chemotherapy. Eighteen months afterwards, an MRI abdomen continues to demonstrate no visible pancreatic mass and the two remaining liver lesions, believed to be scar tissue, remain stable. Her CA 19-9 level remains normal. This appears to be a complete response to FOLFIRINOX/FOLFIRI chemotherapy in a patient with metastatic pancreatic cancer.

scholarly journals Limited benefit of additional contrast-enhanced CT to end-of-treatment PET/CT evaluation in patients with follicular lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gaetano Paone ◽  
Mariana Raditchkova-Sarnelli ◽  
Teresa Ruberto-Macchi ◽  
Marco Cuzzocrea ◽  
Emanuele Zucca ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Metabolic Response ◽  
Residual Disease ◽  
Response Assessment ◽  
Complete Response ◽  
Moderate Increase ◽  
Comparable Rate ◽  
Contrast Enhanced Ct ◽  
End Of Treatment ◽  
Pet Ct

AbstractDespite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS [76% (group of patients with metabolic response) vs 35% (group of patients with residual disease), p = 0.0013] significantly better than ceCT-Based response assessment [75% (group of patients with complete response) vs 53% (group of patients with residual disease), p = 0.06]. Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.

scholarly journals Preliminary Results from a Phase II Study of Response-Adapted Therapy with Copanlisib and Rituximab for Untreated Follicular Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Rahul Lakhotia ◽  
Christopher Melani ◽  
Jagan R. Muppidi ◽  
Stefania Pittaluga ◽  
James D. Phelan ◽  
...  
Keyword(s):  
Supportive Care ◽  
Follicular Lymphoma ◽  
Systemic Therapy ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Complete Response ◽  
Clinical Results ◽  
Circulating Tumor Dna ◽  
Molecular Profile ◽  
Preliminary Results

Introduction Follicular lymphoma (FL) has a highly variable clinical course. Chemoimmunotherapy can induce durable remissions, but ~20% relapse early. The PI3K pathway is central to FL biology and multiple PI3K inhibitors (PI3Ki) are approved for FL, but the molecular profile of tumors most sensitive to PI3Ki is unknown. Further, PI3Ki are dosed indefinitely which contributes to toxicity and cost. Copanlisib is an IV inhibitor of PI3Kα and δ isoforms with high activity in relapsed FL. We hypothesized that patients with FL tumors most sensitive to PI3Ki will achieve deep and durable remissions after a fixed duration of copanlisib-based therapy. Here we report preliminary results of a response-adapted study using copanlisib and rituximab as frontline therapy for FL. Methods Pts with untreated grade 1-2, 3A FL, ≥stage 2, and any tumor burden are eligible if they meet criteria for need of systemic therapy that includes symptoms, increasing size of nodes, critical organ involvement, or impending organ compromise. No prior systemic therapy other than radiation is permitted. Frozen or archival tissue is required. Eligibility includes age ≥18 and adequate organ function unless involved by FL. Active HIV, CMV, Hep B or C, and autoimmune conditions requiring therapy are excluded. All pts receive PCP prophylaxis. Pts first receive copanlisib 60mg on days 1, 8, and 15 of a 28-day window to test activity of monotherapy. On-treatment tumor biopsies are optional after the window. Following the window, pts receive 6 cycles of copanlisib 60mg on days 1, 8, and 15 of a 28 day cycle along with rituximab 375mg weekly x 4 then on day 1 of each cycle. Streck tubes for circulating tumor DNA (ctDNA) are collected weekly during the window, after each cycle, and during surveillance. FDG-PET and CT scans are performed at baseline, after the window, and after cycles 3 and 6 to determine response. Patients with complete response (CR) after 6 cycles stop therapy. Patients with partial response (PR) after 6 cycles receive another 6 cycles of combination therapy with the copanlisib reduced to day 1 and 15 of each cycle. Non-responding patients will receive standard chemotherapy. The primary endpoint is the overall rate of CR with secondary endpoints of safety and duration of CR. Exploratory objectives include identification of a signature that predicts PI3Ki response. Results Ten pts have been enrolled and completed the copanlisib window. Median age was 50y (range, 28-77) including 3 (30%) over age 70. Seven (70%) pts had high-risk FLIPI scores ≥3 and two (20%) pts had Grade 3A FL. Comorbid conditions included prediabetes in 4 (40%) and hypertension in 4 (40%). All 10 (100%) pts had tumor reductions during copanlisib monotherapy with a median reduction of 41% (range 16-62%) (Figure 1). Four pts have completed 6 cycles of copanlisib and rituximab and all 4 (100%) have responded including 2 (50%) who achieved CR. In the two pts who achieved a PR after 6 cycles, one had a 90% tumor reduction and one had only persistent minimal residual disease in the bone marrow by flow cytometry. Toxicity was evaluated in 10 pts across 58 cycles and the most common have included rash (50%), diarrhea (50%) and mucositis (40%) which have all been G1 or G2 and successfully managed with supportive care and did not recur with subsequent cycles. One pt developed grade 3 neutropenia that responded to growth factors and did not recur. Four pts had dose delays due to rash (N=3) and lung infection (N=1). One pt had copanlisib reduced to 45mg due to recurrent rash and elevated liver tests. No pt has discontinued therapy. One pt required oral diabetic medications during therapy that were stopped after therapy completed. One pt had asymptomatic PCP pneumonia diagnosed during the copanlisib window prior to starting prophylaxis that was successfully treated while therapy continued. Conclusion Copanlisib is highly active in untreated FL and the first 10 (100%) patients all had tumor reductions after the first cycle of copanlisib monotherapy, including patients with high tumor bulk. Combination of copanlisib and rituximab can induce complete responses after only 6 cycles and without indefinite therapy. The safety profile includes rash and diarrhea that respond to supportive care and lessen on subsequent cycles. Updated clinical results from this ongoing trial (NCT03789240) along with the molecular profile of FL tumors will be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

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