Who Actually Detects Relapse in Hodgkin Lymphoma: Patient or Physician?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3124-3124 ◽  
Author(s):  
Lynda M. Foltz ◽  
Kevin W. Song ◽  
Joseph M. Connors
Keyword(s):  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Clinical Laboratory ◽  
Initial Therapy ◽  
Primary Treatment ◽  
Physical Exam ◽  
Limited Stage ◽  
Stage Disease ◽  
Therapy Completion

Abstract Background: Few studies have objectively assessed the value of routine clinical, laboratory and radiological evaluation to detect recurrence of Hodgkin lymphoma. The optimal follow up of patients (pts) in complete remission following initial therapy has not been defined. Methods: We identified 99 adult pts with Hodgkin lymphoma, who received treatment and follow up supervised by the British Columbia Cancer Agency and relapsed between Jan 1990 and April 2004. Pts who did not achieve complete remission or had a second hematological malignancy were excluded. Pts were followed with clinical assessment, chest radiograph, CBC and alk phos every 3 m for 2 y, then every 6 m for 3 y, then annually. Routine CT scans were recommended every 6 m for 3 y then annually for 2 y. Relapses were categorized as identified by pt (symptoms, new palpable disease) or by physician (routine physical examination or radiological or laboratory studies in asymptomatic pts). Results: Median age at original diagnosis was 28 y (range 14–73). 86 pts initally had advanced and 13 limited stage disease. Primary treatment was chemotherapy +/− radiation in 93 pts and radiation alone in 6 pts. 10 pts had autologous SCT for primary refractory disease. Median follow up from diagnosis was 82 months (range 12–241). Median time to first relapse from completion of treatment was 14 months (range 2–142). Of the 99 relapses, 75 (76%) were identified by the pt and 24 (24%) by the physician. Pt systemic symptoms of relapse were: fatigue 13 pts; alcohol induced pain 3; weight loss 11; pruritis 9; night sweats 19; fever 6. Local symptoms were shortness of breath 8; chest pain 8; back pain 9; abd pain 3. 29 pts had more than 1 symptom. 44 pts noted a new lymph node or mass and 1 pt had leg swelling. 24 relapses were detected by physician: 14 on CXR, 7 on CT scan, 1 on lymphangiogram and 2 on physical exam. No asymptomatic relapses were identified by laboratory abnormalities alone. 2 of the 13 relapses in pts with initially limited stage disease (18%) were detected by physician (1 CXR and 1 CT chest), vs 22 of 86 (26%) in advanced disease. 78% of relapses occurred within 36 months of completing initial treatment. Patient vs Physician Detected Relapses by Follow up Period Time from therapy completion Patient Detected Relapse Physician Detected Relapse Total # Relapses < 12 months 37 (80%) 9 (20%) 46 12–35 months 19 (61%) 12 (39%) 31 ≥ 36 months 19 (86%) 3 (14%) 22 All Relapses 75 (76%) 24 (24%) 99 80% of relapses within 12 months of therapy completion were detected by pts despite more intensive physician surveillance in this period. The proportion of physician detected relapses was greatest 12–36 months after completion of treatment, possibly due to relapse with more slowly progressive disease amenable to detection on periodic routine testing while it is still being carried on relatively frequently. The 22% of relapses occurring in the period of less frequent surveillance, greater than 3 years after treatment, were primarily detected by pts. Conclusions: 76% of Hodgkin lymphoma relapses were detected by the pt and 78% of relapses occurred within 3 years of therapy completion. Asymptomatic relapse was detected on physical exam and radiological studies but not laboratory testing. The highest proportion of physician detected relapses occurred 12–35 months after treatment. Annual routine follow up beyond 36 months contributed minimally to relapse detection, identifying only 3% of total relapses.

scholarly journals Failure to Achieve CR with First-Line Treatment Is the Primary Cause of Treatment Failure in T-Cell Lymphoma: The Princess Margaret Cancer Centre Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3005-3005
Author(s):  
Umberto Falcone ◽  
Melania Pintilie ◽  
Ri Wang ◽  
Vishal Kukreti ◽  
John G. Kuruvilla ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Primary Treatment ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Limited Stage ◽  
Stage Disease ◽  
First Line Treatment

Abstract Introduction: T-cell lymphomas (T-NHL) represent rarer entities compared to B-NHL, accounting for 5% -10% of NHL in Western countries and 15%-20% in Asia. They are divided into clinico-pathologic subtypes based on etiology, morphology, and clinical behavior. Because of the rarity and the lack of specific histologic features for the different subtypes, the diagnosis is difficult and clinical picture is usually very helpful to establish the diagnosis. We conducted a retrospective analysis of patients (pts) with T-NHL treated at our Centre, with the purpose of studying overall outcome and possible prognostic factors, including histologic subtypes, from our database. Patients and methods: Consecutive T-NHL pts (excluding Adult T-cell leukemia/lymphoma, NK/T NHL, and primary cutaneous T-NHL), receiving primary treatment at the Princess Margaret Cancer Centre (PMCC) between 2001-2014 were included. Data were extracted from a prospective patient database and the medical record regarding baseline characteristics, treatment, response and outcome. Response assessment was with CT imaging as per 1999 Working Group criteria. Results: Of a total of 2155 pts with aggressive histology NHL treated at PMCC between 2001-2014, 2031 pts had B-NHL and 124 (5.7%) T-NHL. Median age was 56 years (18-90), male/female ratio: 2.4; 63% presented with advanced stage (III-IV) disease, 22% had bone marrow involvement; 63% had elevated LDH and 44% had B symptoms. Observed subtypes were: Peripheral T-cell lymphoma, NOS 58 pts (PTCL NOS, 47%), Anaplastic large cell lymphoma, ALK-negative 16 pts (ALCL-ALK-, 13%), ALCL, ALK-positive 22 pts (ALCL-ALK+, 18%), Angioimmunoblastic T-cell lymphoma 13 pts (AITL, 10.5%), Enteropathy-associated T-cell lymphoma 7 pts (EATL, 5.6%), Hepatosplenic T-cell lymphoma 8 pts (HSTCL, 6%). 105/124 pts (85%) received induction chemotherapy; CHOP-like regimens were used in 94 pts (90%), and involved field radiation therapy (RT) was included in primary treatment in 24 pts (19%). Nineteen pts were treated palliatively, 5 pts with RT alone, 14 pts received palliative chemotherapy or supportive care only. Complete response (CR) was obtained in 63/105 pts (60%; Table 2), PR in 2 pts (1.9%) and 40 pts had no response or progressive disease (SD and PD; 38%). Considering together the most common subtypes (ALCL-ALK+/-, AITL, PTCL NOS), CR rate was 84% in limited stage vs 52% in advanced stage disease. Among patients with CR, 24 relapsed (38%). Fourteen pts received autologous stem cell transplant (8 at relapse, 6 for PD); 7/14 (50%) were alive at last follow-up. At a median follow-up of 5.3 years, 57/124 (46%) pts are alive. Cause of death was T-NHL in 50/124 (40%) pts. Two pts died of second malignancy (1.6%). Median overall survival (OS) and progression-free survival (PFS) were 4.57 years (95%CI: 2.23-9.53; 5yOS: 48%) and 1.5 years (0.87-3.17; 5yPFS: 37%), respectively (Table 2). For pts with limited stage disease median PFS was 4.57 years (5yPFS: 49%) and median OS 10.0 years (5yOS: 62%), while for pts with stage III/IV, median PFS was 0.82 years (5yPFS: 31%) and OS 1.81 years (5yOS: 38%). Median OS for pts who did not experience relapse (39/63; 62%) was 13.38 years (95%CI: 9.53-NA; 5yOS: 93%) vs 3.12 years (95%CI: 1.69-4.07 years; 5yOS: 25%) in pts who had relapse after CR1 (p<0.001). Pts failing to achieve CR (PR, SD, PD) had a very poor outcome with median OS 1.15 years (95%CI: 0.62-1.32 years; 5yOS: 17%). For PTCL NOS pts, outcomes were poor while those with ALCL had more favorable results regardless of ALK status (Table 2). Conclusions: Failure to achieve CR with first-line treatment was the main cause of treatment failure in patients with T-NHL treated with anthracycline-based chemotherapy. Patients with limited stage lymphoma and with ALCL ALK+/- subtypes have more favorable outcomes. For PTCL NOS, the most common subtype, and less common entities (HSTCL, EATL), results are poor and new induction strategies are needed. Disclosures Kukreti: Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria.

Early Interim FDG-PET Scan Predicts Outcome in Non-Bulky Limited Stage Hodgkin Lymphoma, but may Not Guide Use of Consolidative Radiotherapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1453-1453 ◽  
Author(s):  
Jeffrey A. Barnes ◽  
Ann S. LaCasce ◽  
Christiana E. Toomey ◽  
Ephraim Hochberg ◽  
Alfred I. Lee ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Complete Response ◽  
Primary Treatment ◽  
Pet Scan ◽  
Rank Test ◽  
Limited Stage ◽  
Interim Pet ◽  
Consolidative Radiotherapy ◽  
Pet Scans

Abstract The standard treatment for limited-stage Hodgkin lymphoma has been combined modality therapy, but late toxicities of radiation have prompted investigation of chemotherapy alone in low risk patients. Initial trials have demonstrated a small increased risk of relapse if radiation is omitted, but no difference in overall survival. We investigated the predictive value of interim FDG-PET (PET) scans in nonbulky limited stage patients, and asked whether PET may guide the use of consolidative radiotherapy for patients in complete remission after chemotherapy alone. A total of 68 patients with nonbulky limited stage disease were identified at our institutions with interim PET performed after 2–3 cycles of chemotherapy. All patients received anthracycline-based chemotherapy with curative intent. PET scan interpretations were extracted by chart review of radiology reports. The median age was 35 (range 18–77). Fifty-nine patients had disease in the neck and mediastinum, 6 had inguinal disease, and 2 in Waldeyer’s ring. Fifty-two patients were stage IIA, 4 were IIB, 10 were IA, and 1 was IB. Radiation was included at the discretion of the treating physician. Complete response required a negative PET scan. The complete response (CR) rate was 88%. Fifty-one patients (75%) had a negative interim PET, and 17 (25%) had a positive interim PET. Interim PET− patients were more likely to achieve a CR at the end of therapy compared to interim PET+ patients (98% vs. 59%; p=0.0001, Fisher’s exact test). At a median follow up of 32 months (range 3–70), the progression-free (PFS) and overall survival (OS) for the entire series were 85% and 100%, respectively. Interim PET− patients had an improved PFS compared to PET+ patients (90% vs. 71%; p=0.032, log rank test). Among the 60 patients who achieved a CR, 50 (83%) were interim PET−, and 10 (17%) were interim PET+. There was no difference in PFS between interim PET+ and PET− patients who achieved a CR. The most important predictor of PFS was achievement of CR at the end of therapy (92% vs. 37%; p&lt;0.0001, log rank test). Consolidative radiotherapy was employed in 18 (30%) CR patients. No difference in PFS was observed based on inclusion of radiation. Among 10 CR patients with a positive interim PET scan, 3 received radiation and 7 did not. All 7 interim PET+ patients treated with chemotherapy alone remained disease free. Eight patients had primary treatment failure (4 partial responses and 4 with progressive disease). Seven of 8 treatment failures were interim PET+. There were 6 relapses in this series occurring at a median of 18 months (range 13–24), 5 occurring in an initially involved field. Five had achieved a CR to initial therapy; 1 had received consolidative radiotherapy. Five of 6 patients had a negative interim PET scan. All patients with treatment failure or relapse were alive at last follow up following salvage therapy. In our series, a positive interim PET scan after 2–3 cycles is predictive of an inferior PFS in patients with nonbulky limited stage Hodgkin lymphoma, but this difference is largely driven by an increase in primary treatment failures among interim PET+ patients. Patients with a positive interim PET who achieve a CR at the completion of chemotherapy have favorable outcomes similar to patients with negative interim PET scans, regardless of inclusion of consolidative radiation. These data suggest that positive interim PET scans denote biologically more aggressive disease but may not be useful in guiding the use of consolidative radiotherapy for patients in complete remission. These observations warrant validation in prospective clinical trials.

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.

1984 ◽  
Vol 2 (10) ◽  
pp. 1115-1120 ◽  
Author(s):  
L J Laubenstein ◽  
R L Krigel ◽  
C M Odajnyk ◽  
K B Hymes ◽  
A Friedman-Kien ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Complete Remission ◽  
Partial Remission ◽  
Kaposi's Sarcoma ◽  
Opportunistic Infections ◽  
Kaposi’S Sarcoma ◽  
Response Duration ◽  
Median Response ◽  
Stage Disease

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.

Limited-Stage Disease: Optimal Use of Chemotherapy and Radiation Treatment

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 321-325 ◽  
Author(s):  
John Radford
Keyword(s):  
Hodgkin Lymphoma ◽  
Radiation Treatment ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Early Years ◽  
Wide Field ◽  
Current Standard ◽  
Limited Stage ◽  
Stage Disease ◽  
Involved Field

AbstractIn the early years of treatment for limited-stage Hodgkin lymphoma there was an understandable focus on disease elimination. This has been replaced by concerns about the amount and balance of different therapies and eventually, as cure rates improve, a desire to individualize management based on risk factors at presentation and response to initial treatment. In limited stage Hodgkin lymphoma, early success was obtained with wide field radiotherapy but later combined modality approaches were employed to overcome the problem of out of field radiotherapy relapses. The acute and delayed toxicity of alkylating agent based therapies led to their replacement with ABVD and concerns about the late toxicity of radiotherapy resulted in smaller field sizes being first assessed in clinical trial and later introduced into clinical practice. The current standard of care of 3 or 4 cycles of ABVD followed by involved-field radiotherapy in clinically staged patients is the culmination of years of work involving many thousands of patients taking part in clinical trials.Our current focus is on the role of PET imaging and whether a response-adapted approach guided by PET can individualize therapy such that radiotherapy and its attendant late toxicity that impacts on future quality of life and survival can be avoided altogether in a subset of patients.

High-Dose Cytoxan, Etoposide, and Cisplatin Followed by Autologous Hematopoietic Cell Transplantation for the Treatment of Hodgkin Lymphoma: A 20-Year Single-Institutional Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1913-1913
Author(s):  
Thomas R. Klumpp ◽  
Moshe C. Chasky ◽  
Robert V. Emmons ◽  
Mary E. Martin ◽  
James L. Gajewski ◽  
...  
Keyword(s):  
Complete Remission ◽  
Total Dose ◽  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Median Number ◽  
High Dose ◽  
Post Transplant ◽  
Grade 3 ◽  
Active Disease

Abstract Since 1988 we have treated 66 patients with relapsed, refractory, or high-risk Hodgkin lymphoma (HD) with high-dose CEP consisting of cyclophosphamide 1,500 mg/m2/day × 4 (total dose, 6,000 mg/m2), etoposide 400 mg/m2 twice daily × 6 doses (total dose, 2,400 mg/m2), and cisplatin 50 mg/m2/day × 3 by continuous i.v. infusion (total dose 150 mg/m2) followed by infusion of autologous peripheral blood stem cells (n=49), bone marrow (n=16), or both (n=1). The patient population included 41 males and 25 females. The median age at transplant was 33 years (range, 17–64 years). Twenty-three patients (35%) had never achieved complete remission prior to transplant, 36 (55%) had previously achieved a complete remission but subsequently relapsed, and 3 (5%) were in first complete remission. Information regarding the disease status at transplant was unavailable for 4 patients (6%). Twenty-seven patients (41%) remain alive and free of any post-transplant relapse or progression as of the most recent follow-up, and an additional 10 patients (15%) manifested active disease post-transplant but are currently in remission following additional post-transplant therapy, yielding a total of 37 patients (56%) currently in CR. In addition, 5 patients (8%) remain alive with active disease, 23 patients (35%) died of progressive disease, and only 2 patients (3%) died of treatment-related causes including diffuse alveolar hemorrhage (1 patient) and hepatic veno-occlussive disease (1 patient). With a median follow-up of 4.4 years among surviving patients, the Kaplan-Meier 5-year estimates for event-free survival and overall survival are 34% and 60%, respectively, and five-year survival was superior among patients who had achieved at least one CR prior to transplant versus patients who had never been in CR prior to transplant (71% versus 43%, p = 0.03). Detailed adverse events data is available regarding all patients transplanted since September 1996: Of these, only 3 (7%) suffered grade 3 or greater pulmonary toxicity, 12 (29%) exhibited grade 3 or higher mucositis, and 10 (24%) had grade 3 or higher nausea or vomiting. The median number of days from transplant to neutrophil recovery (500 cells/uL) was 10 days, whereas the median number of days to platelet recovery (20,000 cells/uL) was 12 days. We conclude that high- dose CEP followed by autologous transplant is an active and well-tolerated treatment program in patients with relapsed or refractory HD. The low incidence of pulmonary toxicity is noteworthy given that a high percentage of patients had been exposed to bleomycin and/or thoracic XRT prior to transplant, and appears to be superior to that reported with conventional CBV-conditioned transplants in patients with HD.

Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Haematological Lymphoid Malignancies: Long Term Follow-up in a Single Centre Series.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4326-4326
Author(s):  
Malek Benakli ◽  
Redhouane Ahmed nacer ◽  
Amina Talbi ◽  
Rachida Belhadj ◽  
Farih Mehdid ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphoid Leukaemia ◽  
Autologous Transplant

Abstract Abstract 4326 Background Patients (pts) with recurrent and refractory haematological lymphoid malignancy (HLM) have a very limited survival expectance. RIC allo-SCT has been proposed as a strategy for retaining the graft versus malignancy effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 32 pts treated by RIC allo-SCT. Patients and methods Between April 2001 and November 2007, 32 pts with HLM underwent RIC allo-SCT with an HLA-identical sibling donor. Fifteen pts with multiple myeloma, 7 pts with Non-Hodgkin lymphoma, 6 pts with Chronic lymphoid leukaemia, 3 pts with Hodgkin lymphoma and 1 pt with Waldenstrom disease. At time of allo-SCT, 10 pts were in complete remission (3 received prior autologous transplant) and 22 in refractory/progressive disease (6 received prior autologous transplant). Median age was 38 years (range, 28-60) and the sex-ratio (M/F) 2,2. Median time from diagnosis to RIC allo-SCT was 18 (range,6-76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 6,2.106/kg (range, 1.9-13,6). Results Neutropenia occurred in all pts (100%) and the median duration of aplasia was 9 (range, 5-16) days. Only 10 pts (31 %) required red blood cells transfusions and 23 pts (71 %) needed platelets transfusions. Acute GVHD was observed in 15 cases (47 %) including 10 cases of grade II-IV. Fifteen pts (75 %) had chronic GVHD, of whom 9 with an extensive form. Four pts (12 %) had CMV reactivation at a median time 60 (range, 52-80) days after transplantation. Six pts (18 %) had late onset relapse at a median time of 13 (range, 4-45) months. TRM was 43 % at one year after RIC allo-SCT. With a median follow-up of 60 (range 18-97) months, 12 pts (37,5 %) are still alive in complete remission with full donor chimerism. Twenty pts (62,5 %) have died (5 early severe infections, 10 GVHD, 3 after relapse, one myocardial infarction, and one accident). Overall and progression-free survivals at 8 years are 31 % and 30 % respectively. Conclusion This study, after a large follow-up, suggests that RIC allo-SCT is a potential therapy for refractory or progressive HLM. However, TRM is still high likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Disclosures: No relevant conflicts of interest to declare.

Functional Imaging in Children and Adolescents with Relapsed or Refractory Hodgkin Lymphoma and Outcome after Autologous Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2264-2264
Author(s):  
Nmazuo Ozuah ◽  
Hisham Dahmoush ◽  
Frederick Grant ◽  
Leslie Lehmann ◽  
Amy Billett ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Functional Imaging ◽  
Salvage Therapy ◽  
Salvage Chemotherapy ◽  
Refractory Disease ◽  
Post Transplant

Abstract Introduction Children and adolescents with Hodgkin lymphoma (HL) have excellent long-term outcomes after combined modality treatment, however ~15-20% will either relapse or have primary refractory disease. (Shankar A, BJH 2014) Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for many pediatric patients with relapsed HL. In adults, achieving a complete remission by functional imaging (FI), particularly positron emission tomography (PET), after salvage chemotherapy is a strong predictor of outcome after ASCT. The majority of published data in pediatric cohorts has employed computed tomography (CT) measurements to assess pre-transplant disease status. We report pre-ASCT FI and clinical outcomes of 49 consecutive children/adolescents, who underwent ASCT for relapsed/refractory HL at our institution. Patients and Methods Following IRB approval, the records of 49 patients with relapsed/refractory HL who received ASCT from January 1, 2001 to December 31, 2014 were reviewed. All had PET (43) or gallium (6) at time of relapse and subsequent time points in disease evaluation pre-ASCT. Available PET scans were reviewed by 2 nuclear medicine physicians, blinded to the clinical data, and assigned Deauville scores. 12 patients who did not have available PET images had outside reports documenting negative PET upon completion of initial salvage therapy. Negative FI was defined as interval resolution of previous gallium avid disease, documented negative PET, or Deauville score ≤ 3. Relapse therapy regimens varied. Patients received standard conditioning regimen with carmustine, etoposide, cytarabine and melphalan(BEAM) followed by stem cell infusion. Post-transplant radiation therapy (RT) was given if no prior RT to the site(s) of relapse. Overall survival (OS) was measured from the date of transplant to death from any cause, progression free survival (PFS) defined as a relapse of HL, with non-HL-related deaths censored. (Lieskovsky JCO, 2004) OS and PFS distributions were examined using Kaplan-Meier curves and the differences between groups were analyzed using the log-rank test and a significant P value < 0·05. Results Median age at time of transplant was 16.4 years; 55% of patients were males. Eighteen (37%) had refractory disease, 22 (45%) relapsed early (3-12 months from completion of primary therapy) and 9 (18%) relapsed late (>12 months).Thirty-one (63%) relapsed within initial RT field. First-line and salvage therapy regimens are detailed in Table 1. Fourteen (27%) received ≥2 salvage therapies; 3 had a 3rd line agent. Nine of the 14 (64%) later achieved negative FI. Three patients with positive PET after initial salvage therapy did not receive a 2nd line regimen. Pre-ASCT,41 patients (84%) had negative FI vs 8 (16%) with positive FI. Eighteen patients (37%) received post-transplant RT; including 5 (64%) in the positive FI group and 13 (32%) in the negative FI group. Median duration of follow up post-transplant was 45.6 months (1-180 months). Forty-five patients were alive and disease-free at last follow up. Post-transplant events included 2 early deaths from transplant-related complications, 1 motor vehicle accident and 1 relapse 6 months post-transplant (pre-transplant Deauville score of 5, death at 12 months). No patient developed a second malignancy. 3-year OS for entire cohort was 92% (95% CI 78-97) with PFS of 98% (95% CI 86-99). 3-year PFS was 100% vs 86% (95% CI 33-98) in negative and positive FI groups respectively (p=0.02). 3-year OS for negative and positive FI patients was 95% (95% CI 82-99) vs 75% (95% CI 31-93) respectively (p=0.06). Complete remission by FI after initial salvage therapy was associated with a trend in OS (97% vs 82% in those with persistent disease) (p=0.08) but not PFS. Extra-nodal disease at relapse, refractory disease and radiation-field relapse had no significant impact on either OS or PFS in a univariate analysis. Cox proportional hazard ratios could not be performed on multivariate analysis given rarity of events. Conclusion Our analysis revealed outstanding outcomes for children/adolescents with relapsed/refractory HL. Negative pre-ASCT PET or gallium was associated with excellent PFS and OS but there were too few relapses to identify the predictive value of pre-transplant FI. Patients who do not achieve complete metabolic response to second line salvage therapy may be candidates for novel approaches. Disclosures No relevant conflicts of interest to declare.

scholarly journals Tumor Associated Antigen Specific T Cells Given in Combination with Nivolumab for the Treatment of Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18 ◽  
Author(s):  
Hema Dave ◽  
Mimi Mai ◽  
Madeline Terpilowski ◽  
Keri Toner ◽  
Maja Stanojevic ◽  
...  
Keyword(s):  
T Cells ◽  
Complete Remission ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Stable Disease ◽  
Peripheral Blood ◽  
Progressive Disease ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background: Hodgkin Lymphoma (HL) Reed Sternberg cells express tumor associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA specific T cells (TAA-T) targeting WT1, PRAME and Survivin were safe and associated with prolonged time to progression in solid tumors (Hont JCO 2019). Hence, we evaluated whether TAA-T cells are safe and elicit anti-tumor effects in patients with relapsed/refractory (rel/ref) HL. We further evaluated the safety of Nivolumab following the TAA-T infusion and its effect on the persistence of the TAA-T cells in vivo. Methods: TAA-T products were generated from patients or healthy donors on 2 trials (NCT02203903; NCT03843294). Thirteen patients underwent procurement for product generation and 10 patients (2 allogeneic; 8 autologous) were infused TAA-T for rel/ref HL or as consolidation after autologous hematopoietic stem cell transplant (HSCT) at cumulative doses ranging from 0.5 X107 to 4 X107cells/m2. Patients were monitored for six weeks for safety and for response until disease progression. Seven patients received Nivolumab starting at 8 weeks after the first TAA-T infusion until disease progression or unacceptable toxicity. Results: TAA-T products (n=10) were polyclonal CD3+ T cells (Median 97%; 80.9-99.5%), comprised predominantly of CD4+ helper T cells (Median 10.5%; 1.74-20%) and CD8+ cytotoxic T cells (Median 70%; 29.3-87.5%). Specificity of TAA-T products was tested using Interferon-ϒ(INFϒ)-enzyme-linked immunospot (ELIspot) assay and defined as ≥ 2x spot-forming cells (SFC)/2.5X105cells against the tumor antigen as compared to irrelevant control antigen Actin(Figure 1). The median TAA specificity of the products was 2 antigens (range 0-3). All products were polyfunctional secreting INF-ϒ and TNF-α upon restimulation with tumor antigens (Fig 1). Median age of patients was 36yrs (range16-53). Patients had received a median 6 lines of therapy including HSCT prior to receiving TAA-T. Median follow-up post TAA-T#1 was 6 months (range 32 days-2.5yrs). There were no dose limiting toxicities observed within the 6 week safety monitoring period. In patients receiving Nivolumab post TAA-T, there were no increased immune related events over expected. One patient had Grade 3 seizures, possibly related to Nivolumab, 2 patients developed hypothyroidism requiring thyroid supplements and one patient developed myositis and discontinued Nivolumab after 5 months. The 2 patients who received TAA-T (1 donor derived and one autologous) as consolidation post HSCT achieved a continued complete remission (CCR) for 2+ years. Of the 8 patients with rel/ref HL at the time of infusion, 1 had disease progression at 6 weeks. He then received Nivolumab off protocol and achieved complete remission (CR) but developed Grade 4 GVHD. The remaining 7 patients had stable disease (SD) at 6 weeks. At a median follow-up of 6 months (32 days-2.5 years), 1 patient had progressive disease(PD) at 3 months, 1 patient had a complete metabolic response at 6 months and proceeded to allogeneic HSCT for definitive cure. 2 patients had PD at 6 months and the other 2 patients continue with SD at 6 months and remain on Nivolumab (Fig 1). All patients with objective responses (stable disease or better) recovered functional TAA-T cells in the peripheral blood at 3 months as detected by anti-Interferon-ϒ ELISPOT and reported as mean SFC/1 X105 cells for WT1(14±SD18.1); PRAME (17.4±15.3) and Survivin (4.5±7) compared to those with progressive disease with mean SFC/1 X105 cells for WT1 1.4(±2.3); PRAME (6.7±15.5) and Survivin (0.8±1.2). To evaluate TAA-T persistence, unique T cell receptor clonotypes defined in the TAA-T product and not present at baseline were detected in the peripheral blood 6 weeks post TAA-T, long-term persistence data and evaluating the effect on the TCR repertoire when adding nivolumab are pending. Conclusion: TAA-T cells given in combination with Nivolumab were safe when administered to patients with rel/ref HL with prolonged clinical responses (ranging from SD to CCR) observed in multiply relapsed patients. Disclosures Glenn: Genentech: Research Funding. Hanley:Mana Therapeutics: Honoraria, Other: Board Member; Cellevolve: Honoraria, Other: Board(Scientific Advisory Board). Bollard:Mana Therapeutics: Other: IP.

scholarly journals Relapse Risk and Loss in Expectation of Lifetime in Young Classical Hodgkin Lymphoma Patients - a Nordic Lymphoma Group Study of 2,582 Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 930-930
Author(s):  
Jorne Lionel Biccler ◽  
Ingrid Glimelius ◽  
Sandra Eloranta ◽  
Knut B. Smeland ◽  
Peter de Nully Brown ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Hodgkin Lymphoma ◽  
Relative Survival ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Event Free Survival ◽  
Free Survival ◽  
Relapse Risk ◽  
Limited Stage ◽  
Stage Disease

Abstract Estimates describing the survival and relapse risk for young classical Hodgkin lymphoma (cHL) patients are of considerable interest. A recent population-based study from British Columbia focused on the evolution of the relative survival and relapse risk given that patients reached certain milestones such as two years of relapse-free survival (Hapgood et al. 2016). The study included patients diagnosed before the year 2000 who were treated with regimens that have since been refined. Using register-data from Denmark, Sweden, and Norway, we investigated cHL survivorship in the era of contemporary treatment by inspecting the evolution of relapse risk and loss in life expectancy. Inclusion criteria were: age at diagnosis 18-49 years; diagnosis year between 2000 and 2013; and treatment with chemotherapy (CT) with or without involved node/field radiation therapy (RT). Event-free survival was measured as the time from diagnosis to progression, relapse, or death, whichever came first. The five-year relapse risks from diagnosis and conditional on reaching event-free survival (EFS) milestones were estimated while taking the censoring and competing risk, death, into account. As a measure of relative survival, we estimated the five-year restricted loss in expected lifetime (5y-RLEL), defined as the numeric difference in the number of days a healthy person and a patient with cHL are expected to survive within the next five years. The 5y-RLEL was estimated taking the censoring into account and was estimated for all patients and for those reaching one (EFS1), two (EFS2), or five (EFS5) years of event-free survival. In total, 2,582 cHL patients were included (Denmark n=863, Sweden n=1,236, Norway n=483). The majority were treated with ABVD (n=1,932). Most limited stage (IA-IIA) patients were treated with 2-4 courses of CT and RT with dosage up to 30Gy The majority of the advanced stage (IIB-IV) patients were treated with 6-8 courses of CT +/- RT. A fraction of the patients (n=306) were treated with 6-8 BEACOPP 14 or escalated BEACOPP. Advanced stage patients receiving BEACOPP more often had adverse risk criteria including involvement of the bone-marrow (27% vs 6%) and/or other extranodal sites (60% vs 34%) than advanced stage patients treated with 6-8 cycles of ABVD. The five-year OS was 95.2% (95% CI 94.4 - 96.1) and the five-year risk of relapse was 13.4% (95% CI 12.1-14.8). The dynamic evolution of the five-year relapse risk is shown in Figure 1A and the 5y-RLEL estimates in Figure 1B. For patients reaching the EFS2 and EFS5 milestones, five-year relapse risks were 4.2% (95% CI 3.8 - 4.6) and 0.8% (95% CI 0.8 - 0.9) (Figure 1A), respectively. From diagnosis, the five-year relapse risk for advanced stage patients was twice as high as for limited stage patients, however the difference decreased among patients reaching later EFS milestones and was small after EFS3 irrespective of stage (2.5% [95% CI 2.1 - 2.9] for advanced stage disease vs. 2.0% [95% CI 1.6 - 2.4] for limited stage disease) (Figure 1A). The five-year relapse risk for advanced stage patients treated with 6-8 courses of BEACOPP was comparable to that of advanced stage patients treated with 6-8 courses of ABVD despite more adverse risk criteria among the BEACOPP treated patients (Figure 1A). The 5y-RLEL was limited, e.g. within the first five years post-diagnosis the HL patients were expected to live 46 days (95% CI 35 - 54) less than what was expected for the background population (Figure 1B). Patients reaching the EFS2 milestone had a 5y-RLEL of 13 days (95% CI 7 - 20) and for patients reaching the EFS5 milestone, the 5y-RLEL was 8 days (95% CI 2 - 14) (Figure 1B). Limited stage patients who remained event-free two years post-diagnosis had a minimal 5y-RLEL of 2 days (95% CI -4 - 7) (Figure 1B). By reporting five-year relapse risk and loss of life expectancy overall and conditioned on years in remission, we provide relevant patient-centred prognostic measures for young contemporarily treated cHL patients. The results are reassuring and indicate that limited stage patients who remain event-free two years post-diagnosis have a future life expectancy in line with HL-free individuals. Additionally, irrespective of risk group, the five-year relapse risk was minimal once three years of event-free survival was reached. This information should be taken into account in future surveillance programs. Disclosures Eloranta: Janssen Pharmaceuticals: Other: S Eloranta is currently employed as a project coordinator and her salary is funded via a public-private real world evidence collaboration between Karolinska Institutet and Janssen Pharmaceuticals. Fosså:Janssen Pharmaceuticals, Inc.: Honoraria. Ekstroem Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.

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