F‐18 <scp>FDG</scp>‐<scp>PET</scp> predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem‐cell transplantation for relapsed and refractory <scp>H</scp>odgkin lymphoma

Gentzler, Ryan D.; Evens, Andrew M.; Rademaker, Alfred; Weitner, Bing Bing; Mittal, Bharat B.; Dillehay, Gary; Petrich, Adam M.; Altman, Jessica K.; Frankfurt, Olga; Variakojis, Daina; Singhal, Seema; Mehta, Jayesh; Williams, Stephanie; Kaminer, L.; Li, Gordon; Winter, Jane N.

doi:10.1111/bjh.12824

Cited by 46 publications

(33 citation statements)

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“…There is extensive literature demonstrating the prognostic significance of CR as measured by functional imaging prior to ASCT, as shown in studies combining both primary refractory and relapsed patients (Jabbour et al, 2007;Castagna et al, 2009;Arai et al, 2010;Mocikova et al, 2011;Smeltzer et al, 2011;Akhtar et al, 2013;Cocorocchio et al, 2013;Nieto et al, 2013;Sucak et al, 2013;Gentzler et al, 2014). Jabbour et al (2007) reported on a retrospective cohort including 66 primary refractory patients, finding a 3-year progressionfree survival (PFS) of 69% for those with negative functional imaging (both PET and gallium scans) compared to 23% with positive scans prior to transplant.…”

Section: Discussionmentioning

confidence: 99%

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Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Shah

Bantilan

Verwys

et al. 2015

Blood

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Introduction: Limited information exists on the best treatment strategy for Primary Refractory (ref) Hodgkin Lymphoma (HL). For the past 20 years, we have treated patients (pts) on sequential ifosfamide, carboplatin, etoposide (ICE)-based clinical trials with the intent to undergo high dose therapy (HDT) and autologous stem cell transplantation (ASCT). As previously reported (Moskowitz, Blood 2010) and confirmed by other centers, a negative PET scan prior to ASCT predicts for marked improvement in outcome in pts with relapsed HL. We aimed to identify risk factors that predict PET response to salvage chemotherapy in ref HL and evaluate outcomes following HDT and ASCT in this patient population. Methods: From 10/1/94 to 7/10/15, 192 ref HL pts were treated on sequential trials at MSKCC. Demographic and clinical factors were collected. Event free survival (EFS) and overall survival (OS) were calculated from the date of histologic confirmation of ref disease, estimated by Kaplan-Meier method, and compared by the log rank test. Events included relapse or death. Cox regression was used for the multivariate regression model. Patients were selected to receive a radiation-based conditioning regimen if all sites of nodal disease could be encompassed into a radiation field. Results: Patient characteristics included a median age of 31 (range 14-79) with 54% female. B symptoms, extranodal disease, stage IV disease, and disease bulk > 5cm were present in 31%, 48%, 44%, 40%, respectively. In the intent-to-treat (ITT) population, 41% had a positive post-salvage PET scan. As analyzed by ITT, median EFS was 8.9 years with a median OS of 10.4 years. On multivariate analysis, the presence of B symptoms and bulk >5cm at documentation of ref disease predicted for a reduced chance of achieving a negative PET after salvage therapy, with an odds ratio (OR) of 2.03 for B symptoms and 2.13 for bulk >5cm. For the 169 (88%) transplanted patients, 68% had a negative pre-ASCT PET. Radiation based conditioning was used for 70% of the pts. Median EFS was 12.8 yrs and median OS was not reached with a median follow-up of 3.6 yrs (range, 0.55 to 18.04 yrs) for the surviving patients (Figure 1). On multivariate analysis, both stage (IV vs I-III) and persistent PET abnormality pre- ASCT correlated with a shorter EFS. A risk stratification model was created and pts could be divided into 4 groups. 1) stage I-III disease and a negative PET pre-ASCT, the median EFS was not reached; 2) stage I-III disease and a positive PET pre-ASCT scan-the OR of an event was 4.04 (95% CI 1.93 to 8.45) with the median EFS not reached, 3) Stage IV disease and a negative PET pre-ASCT, the OR was 3.78 (95% CI 1.64 - 8.74) with a median EFS of 8.9 yrs, 4) Stage IV disease and a positive PET pre-ASCT, the OR was 8.22 (95% CI 3.99 to 16.94) with a median EFS of 0.9 yrs (Figure 2). Conclusions: B symptoms and bulk >5cm predicted for residual PET avidity after salvage therapy in ref HL. Persistent PET abnormality pre-ASCT and stage were risk factors for earlier relapse and death and can be used to prognosticate survival. Further studies are needed to determine optimal therapy for patients with multiple risk factors. Figure 1. EFS for the Transplanted Patients Figure 1. EFS for the Transplanted Patients Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Disclosures Moskowitz: GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Shah

Bantilan

Verwys

et al. 2015

Blood

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“…In particular, the positron emission tomography (PET) status at transplantation, which mirrors the efficacy of the salvage regimen, is fundamental in assessing patients’ prognosis, as progression‐free survival (PFS) rates are significantly better (i.e. more than doubled at 4 and 5 years) in patients who are transplanted with a negative PET scan, compared to those who still display PET positivity (Moskowitz et al , 2010a; Moskowitz et al , 2010b, ; Mocikova et al , ; Smeltzer et al , ; Devillier et al , ; Akhtar et al , ; Gentzler et al , ). Importantly, no differences in outcome have been reported for patients needing 2 salvage regimens instead of only one, provided the pre‐autologous PET scan is negative (Moskowitz et al , ).…”

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The role of transplantation in Hodgkin lymphoma

Broccoli

Zinzani

2018

Br J Haematol

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Summary Autologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first‐line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti‐programmed death 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post‐autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high‐risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post‐autologous salvage treatments still remain to be determined.

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“…There is extensive literature demonstrating the prognostic significance of CR as measured by functional imaging prior to ASCT, as shown in studies combining both primary refractory and relapsed patients (Jabbour et al , ; Castagna et al , ; Arai et al , ; Mocikova et al , ; Smeltzer et al , ; Akhtar et al , ; Cocorocchio et al , ; Nieto et al , ; Sucak et al , ; Gentzler et al , ). Jabbour et al () reported on a retrospective cohort including 66 primary refractory patients, finding a 3‐year progression‐free survival (PFS) of 69% for those with negative functional imaging (both PET and gallium scans) compared to 23% with positive scans prior to transplant.…”

Section: Discussionmentioning

confidence: 99%

“…Knowledge of the clinical characteristics of primary refractory HL is limited, as these patients are often not differentiated from relapsing HL in the medical literature. Ten studies published since 2007 included a total of 372 primary refractory patients (Jabbour et al , ; Castagna et al , ; Arai et al , ; Mocikova et al , ; Smeltzer et al , ; Akhtar et al , ; Cocorocchio et al , ; Nieto et al , ; Sucak et al , ; Gentzler et al , ). While first‐line treatment was quite uniform, the majority having received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), the salvage and conditioning prior to ASCT differed considerably, and incorporated radiation therapy as well.…”

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Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation

et al. 2016

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Summary We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8·9 years and OS 10·4 years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk ≥5 cm predicted for positive FI, with odds ratios of 2·15 and 2·03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre-ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3·6 years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre-ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P < 0·001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors.

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F‐18 FDG‐PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem‐cell transplantation for relapsed and refractory Hodgkin lymphoma

Cited by 46 publications

References 30 publications

Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

The role of transplantation in Hodgkin lymphoma

Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation

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