scholarly journals Progression Free Survival (PFS) Analysis of Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone: A Quadruplet Intensified Treatment for Transplant Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3943-3943
Author(s):  
Edvan De Queiroz Crusoe ◽  
Joanna Leal ◽  
Marco Aurelio Salvino ◽  
Larissa Ferreira Lucas ◽  
Juliana Andrade Santos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cell ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Investigational Agent ◽  
Pet Ct ◽  
One Year

Abstract Background: Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that Dara and CTd combination could be safe and allow deeper activity as an alternative protocol. Aims: The aims of this analysis were to evaluate Progression Free Survival (PFS) of Dara-CTd treatment and minimal residual disease (MRD) after one year of Dara maintenance. Primary endpoint of the study was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. The MRD was evaluated by next-generation flow (NGF) based and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Data cut-off was June 15, 2021. Results: The first pts was enrolled in November 2018. A total of 24 pts were included, the median age being 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 20 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and six (30%) pts needed plerixafor use. By ITT analysis after a median follow up of 20 months the PFS at 12 and 18 months was 86%. No PFS difference was observed between different subgroups. Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 13 (76%) obtained MRD negativity by NGF and 10 (58%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Six pts completed one year of maintenance and five of them (83%) still MRD negativity by NGF. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Two pts have discontinued treatment due to progression - 1 before ASCT e 1 during maintenance. The most common adverse events (AEs) grades 3 and 4 were neutropenia (n = 12), infusion reaction (n = 7), neuropathy (n = 6), lymphopenia (n = 4), infection (n = 3), hypertension (n = 1) and rash (n = 1). Summary/Conclusion: The Daratumumab - CTd protocol is an active regimen capable of producing deep and sustainable responses and improve the PFS of NDMM TE pts with a favorable safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding. Hungria: Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria; Abbvie: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel .

scholarly journals Preliminary Results of Daratumumab, Cyclophosphamide, Thalidomide and Dexamethasone: A Quadruplet Intensified Treatment for Newly Diagnosed Multiple Myeloma (NDMM) Transplant Eligible (TE) Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Edvan De Queiroz Crusoe ◽  
Marco Aurelio Salvino ◽  
Sarah Queiroz Silva ◽  
Herbert Henrique de Melo Santos ◽  
Allan de souza Santos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Safety Profile ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Performance Status ◽  
New Drugs ◽  
Open Label ◽  
Post Transplant ◽  
Investigational Agent ◽  
Pet Ct

Background: The inclusion of the CD38-targeting antibody daratumumab (Dara) increases the depth and duration of the response, as demonstrated by Dara-VTd and Dara-VRd protocols to treat NDMM - TE patients (pts). However, the access to new drugs is a challenge for some countries in Latin America. There are many induction protocols and one of the most used inductions worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the combination of daratumumab and CTd (Dara-CTd) could be safe and allow deeper activity in NDMM TE pts. Objective: The primary endpoint was the attainment of VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow by the EuroFlow® and PET-CT and the safety profile. An exploratory endpoint was the analysis of the immunologic change in the lymphocyte profile during the treatment. Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: NDMM TE, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol scheme was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, Dex at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after transplant and all patients received up to four 28-day consolidation cycles: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. All patients received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Results: The first patient was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 38 - 67 years), 18 (85%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, 18 pts have completed induction, 12 have received transplants and 10 have completed D+90 post-transplant assessment. In an intention to treatment analysis, after the end of induction (cycle 4), 17 (95%) of the pts obtained > PR and 7 (33%) obtained VGPR or better. Ten patients have completed two consolidation cycles after transplant and 100% obtained > VGPR as best response, 8 (80%) obtained MRD = -10-5 negative remission by flow cytometry and 6 (60%) had negative PET-CTs. Five (50%) patients had both flow and PET-CT negativity. Two patients died from infection, one post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common non-hematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 6), infection (n = 2), hypertension (n = 1) and rash (n = 1). Conclusion: This is the first study that combined daratumumab with CTd as induction for NDMM TE patients. This preliminary data has shown that the association of Dara-CTd achieved a deep response with a safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding.

Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy with Interleukin-2 Versus Observation for Patients with Non-Hodgkin’s Lymphoma: Results of a Phase III Randomized Trial by the Southwest Oncology Group (SWOG 9438).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 326-326 ◽  
Author(s):  
John A. Thompson ◽  
Richard I. Fisher ◽  
Michael L. LeBlanc ◽  
Joseph M. Unger ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Grade ◽  
Survival Estimate ◽  
Free Survival ◽  
Post Transplant ◽  
Total Body

Abstract Purpose: To determine the effect of post-transplant immunotherapy with Interleukin-2 (IL-2) on the progression-free and overall survival of patients with non-Hodgkin’s lymphoma (NHL) after autologous stem cell transplantation and to assess the toxicity of post-transplant IL-2 therapy. Patients and Methods: Patients with previously treated low, intermediate, or high grade NHL (except Working Formulation Groups A and I) were treated with high-dose cyclophosphamide, etoposide, and total body irradiation (TBI) and an autologous peripheral blood stem cell transplant (PBSCT). Twenty-eight to 80 days after PBSCT, patients were randomized to treatment with IL-2 versus observation. Results: Between January 1995 and July 2004, three hundred ninety-four patients with low-grade (n=61) or intermediate-high grade NHL (n=315) were registered at one of 39 SWOG transplant centers. One hundred ninety patients did not proceed to randomization, because of patient refusal (44), grade V toxicity (30), disease progression (28), toxicity (28), or other reasons. Two hundred four patients were randomized to treatment with continuous infusion intravenous IL-2 (9 ×106 units/m2/day for four days followed five days later by 1.6 ×106 units/m2/day for 10 days) versus observation. The 4-year progression-free survival estimate for all eligible patients is 34%, and the 4-year overall survival estimate is 52%. There was no difference in progression-free survival (hazard ratio (HR) of IL-2 to observation = 0.90; p = 0.56) nor in overall survival (HR of IL-2 to observation = 0.88; p = 0.55). There were no deaths related to IL-2 treatment. Grade IV IL-2-related toxicities included hematologic (n=10), cardiovascular (4), renal/bladder (2), flu-like symptoms (1), lung (1), metabolic (1), and neurologic (1) and were reversible in all cases. Conclusions: These results confirm earlier SWOG findings that a regimen of cylophosphamide, etoposide and TBI followed by PBSCT can be administered to patients with relapsed or refractory NHL with acceptable toxicity and with encouraging progression-free and overall survival. Post-transplant therapy with IL-2 given at this dose and schedule of administration had no significant effect on post-transplant relapse, progression-free survival or overall survival.

scholarly journals Case series: MRD negativity assessment using 11C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110303
Author(s):  
Cheong Ngai ◽  
Shaji Kumar ◽  
Garrett Chi-lai Ho ◽  
Sirong Chen ◽  
Chor-sang Chim
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Positron Emission ◽  
Pet Ct ◽  
Subsequent Relapse

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.

Prevention of Graft-Versus-Host Disease (GVHD) with Tacrolimus after Allogeneic Grafting for Hematological Malignancies Following Sub-Myeloablative Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5321-5321
Author(s):  
Joseph Fay ◽  
Giovanna Saracino ◽  
Edward Agura ◽  
Brian Berryman ◽  
Luis Pineiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Post Transplant

Abstract Severe acute or chronic GVHD following allogeneic hematopoietic stem cell transplantation therapy (HSCT) has a deleterious effect on the successful treatment of hematological malignancies. We have retrospectively studied mycophenolate mofetil (MMF) and tacrolimus (FK) or cyclosporine (CSA) following allogeneic HCST in the prevention of GVDH and the induction of immune tolerance in 93 patients with hematological malignancies using non-myeolablative pre-transplant conditioning. In the current study, there were 35 patients with leukemia, 36 patients with lymphoma, 12 patients with myelodysplastic syndrome or a myeloproliferative disorder and 10 patients with multiple myeloma. There were 63 women and the median age was 42 (15–75) years. Twenty patients had relapsed after previous autologous or allogeneic HSCT and 45 patients were older than 59 years. The remaining patients had co-morbid medical conditions that precluded the use of chemotherapy/radiotherapy dose-intensive pre-conditioning. Conditioning prior to allogeneic HSCT (94 blood stem cell grafts and 1 marrow graft) was fludarabine (90 mg/m2 in three daily doses) and TBI (200cGy) in 86 patients, fludarabine (120 mg/m2 in 4 daily doses) and cyclophosphamide (50mg/kg) in 5 patients, and TBI (200 cGy) only in 4 patients. Forty-three patients received sibling and 50 unrelated grafts. Median follow-up post transplant is 3.0 (0.2–6.1) years. Five (5.3%) patients did not experience sustained hematological chimerism post-transplant. MMF and FK were administered to 33 recipients and MMF and CSA to 60 recipients. The dose and schedule of MMF, CSA and FK have been published (Laport et al. Blood, 2006 and Fay et al. Blood, 1996.) There was no difference in the degree of HLA mismatching between the two groups of patients. Cumulative incidences were used to estimate the incidence of acute and chronic GVHD, all deaths and disease progressions not related to GVHD being considered as the competing events. The Gray test was used to compare cumulative incidences between groups. The unadjusted cumulative incidence of grade III–IV acute GVHD that required oral or systemic corticosteroid therapy, was 54% (95% CI, 40%–68%) in evaluable patients who received CSA in contrast to 38% (95% CI, 18%–58%) in patients who received FK (p-value=0.25). Furthermore, the unadjusted cumulative incidence of extensive chronic GVHD at 1 year was 45% (95% CI, 32%–58%) for CSA versus 34% (95% CI, 14%–54%) for FK (p-value=0.48). Progression-free survival between patients who received FK or CSA at the time of the analysis of this study is similar (p-value=0.6191). The progression-free survival at 1 year was 43% (95% confidence interval [CI], 24%–62%) for CSA versus 43% (95% CI, 31%–55%) for FK. Analyses of the overall morbidity and the incidence of infectious complications between the 2 groups are ongoing. FK combined with MMF may be superior to CSA and MMF in the prevention of GVHD post sub-myeloablative allogeneic HSCT therapy for hematological malignancies and FK may result in improvement of treatment outcome. We believe further study is warranted.

Pilot Evaluation of the Value of FDG PET-CT after One and Two Cycles of Salvage Chemotherapy in Relapsed/Refractory Aggressive Non-Hodgkin’s and Hodgkin’s Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4951-4951
Author(s):  
Andrew Hodson ◽  
Tara Barwick ◽  
Brigitta Marson ◽  
Nick Maisey ◽  
Kavita Raj ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Escalation ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Pet Ct ◽  
Risk Of Relapse

Abstract Introduction The currently accepted standard of care for patients with relapse/refractory NHL is dose escalation and consolidation with Stem Cell Transplantation. The ability to predict those patients who may benefit or not from this approach would be beneficial. Whole-body Positron Emission Tomography using 18F-fluorodeoxyglucose (FDG) is now recognised to have predictive ability in those patients at high risk of relapse and shortened overall survival in De novo High grade lymphoma. In the salvage setting it is unknown whether the appearance of PET scan after 1 cycle of salvage treatment may predict similarly for outcome post transplant and whether early scanning is indicated before cycle 2 salvage chemotherapy. Aim: The aim of this study is to assess whether the PET-CT after one cycle or two cycles of dose escalation was predictive of outcome in patients with relapse/refractory NHL. Methods: We collected the data prospectively of all patients with relapsed or refractory aggressive NHL or HD treated in our institution over a 2 year period who were considered suitable for salvage therapy followed by Stem Cell Transplantation. We identified 14 male and 10 female patients with a mean age of 44 years (range 24–66). 12 patients had disease refractory to first line treatment and 12 patients had relapsed disease with a median interval from completion of treatment to relapse of 20 months (range 2–60). All patients were initially treated with DHAP as salvage therapy.22/24 patients proceeded to a stem cell transplant. 16/22 had an autologous transplant conditioned with BEAM and 6/22 had allogeneic transplants.FDG PET- CT scans were performed (all positive) prior to salvage chemotherapy and then assessed after 1 cycle of salvage chemotherapy and then after the second cycle using a 5 point visual scoring system as follows: CMR - no uptake at disease sites, MRU1 – visually uptake below level of mediastinum, MRU2 – visually between mediastinum and liver Stable/persistent metabolically active disease and Progressive disease (either new lesions or increased uptake in the same sites. Results FDG-PET Data was collected from 24 patients (14 male and 10 female) and read by two independent observers. The patients had the distribution shown in table: Visual response criteria Appearance PET 1 : Patient Numbers Appearance PET 2 : Patient Numbers CMR 1 6 MRU1 0 2 MRU2 1 3 Stable/persistent 16 5 Progressive 6 8 The median progression free survival of the patients with progression after one cycle of chemotherapy was 1.5 months with 3/6 deaths. Progression on PET1 was seen only in refractory cases pre salvage and was associated with a significant risk of relapse (p=0.014). The median progression free survival of the patients with stable disease after one cycle was 9.5 months. After two cycles of chemotherapy the median progression free survival of patients with CMR/MRU1/MRU2 was 9 months, compared with stable disease of 8 months and progressive disease 6 months. Conclusions: Patients with progressive disease on PET after one cycle of chemotherapy have a poor outcome with 50% early deaths and would be candidates for targeted/experimental therapies. Longer follow up will be required to assess the significance of stable or persistent disease on PET after one cycle and two cycles of salvage chemotherapy.

Multiparameter Flow Cytometry Remission Is the Most Relevant Prognostic Factor for Multiple Myeloma Patients Who Undergo Autologous Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 737-737
Author(s):  
Bruno Paiva ◽  
Maria-Belén Vidriales ◽  
Jorge Cerveró ◽  
Gema Mateo ◽  
Jose J. Pérez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Plasma Cells ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Multiparameter Flow Cytometry ◽  
Cell Transplant ◽  
Post Transplant

Abstract Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol (VBMCP/VBAD induction plus autologous stem cell transplant [ASCT]). MRD status by MFC was determined at day 100 post-ASCT. Persistent myelomatous plasma cells (MM-PCs) were detected by MFC in 170 patients (58%), who were considered MRD-positive. Progression-free survival (PFS; median 71 vs 37 months, P < .0001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD-negative versus MRD-positive at day 100 post-ASCT, with a 5-year PFS rate of 60% and 22% (P < .0001), respectively. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation (IFx) negative complete response post-ASCT. The 5-year PFS rate was 62% in MRD-negative patients (n=94) versus 30% in MRD-positive patients (n=53; P < .0001), and the respective 5-year OS rates were 87% versus 59% (P = .009). Moreover, MRD− IFx− and MRD− IFx+ patients had significantly longer PFS than MRD+ IFx− patients (median 71, 65, and 37 months, respectively, P = .0002). By multivariate analysis, only MRD status by MFC at day 100 post-ASCT and FISH cytogenetics were identified as independent prognostic factors for PFS, and only MRD status by MFC and age were identified for OS. The relative risks of progression and death among MRD-positive versus MRD-negative patients were 3.64 (P = .002) and 2.02 (P = .02), respectively. Finally, a subgroup of 157 patients in which MRD information was available both pre- and post-ASCT were analyzed. Patients who were MRD-positive both pre- and post-transplant (n=93) had the worst prognosis; patients who were MRD-positive pre-ASCT but improved to MRD-negative post-ASCT (n=48) had an intermediate prognosis, and patients who were MRD-negative both pre- and post-transplant (n=16) had the best prognosis. The 5-year PFS and OS rates in these three prognostic subgroups were 25%, 57%, and 80%, respectively (P = .0001), and 59%, 78%, and 100%, respectively (P = .06). In summary, our results show that MRD evaluation by MFC is a very useful technique to identify patients at different risk of progression. This type of analysis, particularly when performed post-ASCT, may contribute to the design of patient-specific maintenance treatment approaches, as well as the evaluation of the potential benefits of consolidation therapies.

Response-Adjusted Transplantation in Primary Resistant and Relapsed Hodgkin Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 336-336 ◽  
Author(s):  
Kirsty Thomson ◽  
Irfan Kayani ◽  
Kirit M Ardeshna ◽  
Emma Morris ◽  
Rachael Hough ◽  
...  
Keyword(s):  
Residual Disease ◽  
Autologous Transplantation ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Unrelated Donor ◽  
First Line ◽  
Free Survival ◽  
Pet Ct ◽  
Donor Lymphocytes

Abstract Abstract 336 Therapeutic options for patients with primary resistant or relapsed Hodgkin Lymphoma (HL) have remained largely unchanged for the past 20 years, comprising salvage chemotherapy consolidated by autologous transplantation. Newer agents such as brentuximab vedotoxin may increase response rates, and are being evaluated in the maintenance setting after transplantation. For patients with chemosensitive disease, autologous transplantation confers 5yr progression-free-survival rates of 40–50%. Prognosis is worse in primary resistant or early relapsing disease (within 12 months of primary therapy). Functional imaging also provides prognostic information. Patients with metabolic complete response (mCR) prior to autograft have progression-free survival (PFS) rates in excess of 70% at 3–5yrs, whilst in those with chemosensitive disease (CR/PR) but residual metabolically active lesions these figures drop to 25–30%. The feasibility of performing allogeneic hematopoietic stem cell transplants in patients with HL using reduced intensity conditioning is well established. However, reduced non-relapse mortality rates have been associated with increased relapse, which is now the major cause of treatment failure. Registry data suggest the importance of dose intensity in determining relapse risk. Consideration of transplantation earlier in the disease pathway may improve the tolerability of increased dose intensity. We evaluated the feasibility of a response-adjusted transplantation strategy, based on assessment of disease status by FDG-PET-CT following salvage chemotherapy. Between November 2007 and December 2010 we treated 61 patients with primary refractory or relapsed HL at our institution. Patients were restaged following 1 line of salvage. Those in mCR were consolidated with a BEAM autograft, whilst non-progressive patients with <mCR were offered a BEAM-alemtuzumab allograft. Those with progressive or bulky residual disease were given further salvage until they demonstrated stable disease or better, at which point they were eligible for an allograft. Patients were monitored following the allograft for lineage-specific chimerism and restaged by PET-CT, and received dose-escalating donor-lymphocytes from 6 months post-transplant for mixed chimerism or residual disease/progression. 53/61 (87%) patients achieved sufficient response and were fit for high-dose therapy. 28 patients proceeded to autograft and 25 to allograft (8 related donor, 12 HLA-matched unrelated donor, and 5 HLA-mismatched unrelated donor). The majority had received ABVD as first-line therapy (n=48), and ESHAP as first-line salvage (n=48). 21 of those proceeding to allograft received mini-BEAM as additional salvage. The median number of lines of salvage was 2 (1–8) in the allograft cohort. 12/13 ‘late' relapses, 5/9 ‘early' relapses and 11/31 primary resistant cases received an autograft. The median age at transplant was 32 in both groups (range 18–66 for autograft vs 16–50 for allograft). Median follow-up is 2.5 vs 2.3 years respectively (range 0.5–3.6yrs in both). Outcomes in the autograft group were understandably good. NRM was 4%, and relapse incidence 11%. 3yr OS and PFS were 92% and 85% respectively. Outcomes following allografting in the higher risk cohort were also encouraging. All engrafted. NRM was 8% and relapse incidence only 16%, with all relapses occurring within 9 months of transplantation. 4 patients received donor-lymphocytes for relapse. All responded and 3 (all CR) are maintained. 3yr OS, PFS and ‘current' PFS are therefore 88%, 71% and 84% respectively. 4 patients developed grade II and 2 patients grade III acute graft-versus-host disease, and no patients were taking immune suppressants beyond 18 months after transplantation. The combined 3yr outcomes for all 53 transplanted patients are 90% OS, 78% PFS and 84% cPFS. In conclusion, the data demonstrate favorable survival outcomes for the entire cohort of primary resistant and relapsed patients. They illustrate that selected patients with primary resistant and early relapsed disease may do well following autografting, but more strikingly that those predicted to have poor outcomes based on functional imaging may have very favorable outcomes following alemtuzumab-based allografting with aggressive post-transplant immune modulation. The data now form the basis for 2 national UK studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Predictive Value of PET/CT for Post-Transplant Outcomes in T Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2914-2914
Author(s):  
Nancy Kaddis ◽  
Eric D Jacobsen ◽  
Ailbhe O'Neill ◽  
Nikhil Ramaiya ◽  
Robert A. Redd
Keyword(s):  
Predictive Value ◽  
Progression Free Survival ◽  
Ct Images ◽  
Negative Group ◽  
Free Survival ◽  
Positive Group ◽  
Post Transplant ◽  
Pet Ct

Abstract Objective 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used routinely for response assessment and treatment decision making in Hodgkin lymphoma and B cell non-Hodgkin lymphoma. The predictive value of PET/CT in patients with peripheral T-cell lymphomas (PTCL) is not well defined. We performed a retrospective single institution analysis to determine the utility of pre-transplant PET/CT to predict outcomes following autologous stem cell transplant (ASCT) for PTCL. Materials and Methods PET/CT patient population We screened the Dana-Farber Cancer Institute database for patients undergoing ASCT between 2005 and 2015 and identified 109 PTCL patients. Patients had PET/CT performed within 3 months prior to transplant and follow up PET/CT within one year of ASCT. 38 patients met the inclusion criteria (17 women, 21 men, mean age at transplant 56 years, SD ±14.6, range 22-73). Image interpretation The FDG-PET/CT images were reviewed on HERMES GOLD (Hermes Medical Solutions AB, Stockholm, Sweden) workstation by a radiologist (AON) blinded to clinical details. Pre-transplant PET/CT images were read initially and then one week later the post-transplant PET/CT images were read with the reader blinded to the pre-transplant PET/CT findings. The Deauville five-point scale was used for staging and assessment of treatment response and recurrence. A Deauville score of 3 or less was considered a complete response (CR). Results There was mean of 1.3 months between the initial PET/CT and transplant. Mean of 5 months between transplant and follow up PET/CT. A total of 30 patients had a CR on pre-transplant PET/CT. There were 8 patients with persistent sites of FDG uptake on PET/CT with Deauville 4 (n=4), Deauville 5 (n=2) consistent with partial response to treatment. Pre-transplant PET/CT did not correlate with long term survival outcomes including 3-year PFS in our data; a negative pre-transplant PET/CT was not associated with improved 3-year PFS as compared to a positive pre-transplant PET/CT. A total of 26 patients (68%) had no evidence of disease on post-transplant PET or negative post treatment PET/CT. Of those, 23 (88%) had a 3 -year progression free survival, 13 (50%) had a 5-year progression free survival, and 5 (19%) had died of recurrent disease at the time of our analysis. On post-transplant, a total of 12 patients had positive PET/CT with 6 achieving partial remission and 6 having progressive disease on post-transplant PET/CT. In terms of outcome, the 3-year PFS for the PET positive group was 42% (5/12). Of those, 2 (17%) had durable 5-year PFS with treatment after transplant while the other 10 (83%) eventually died of their disease. The 3-year PFS rate in the PET negative group was 88% (23/26) (95% CI: 70 - 98%) and 42% (5/12) (95% CI: 15 - 72%%) for PET positive group. The difference in the 3-year PFS in the PET negative group is significantly larger than that of the PET negative group (p<0.005). The 5-year PFS in the PET negative group was 50% (13/26) and 17% (2/12) for the PET positive group with a marginally significant difference (p=0.08) Conclusions: Patients with a negative post-transplant PET/CT had a 3-year PFS of 88% and 5-year PFS of 50% compared to a 3-year PFS of 42% and a 5-year PFS of 17% in patients with a positive post-transplant PET/CT. This suggests that post-transplant PET/CT is a clinically meaningful predictor of long-term disease-free survival. The PFS data in the patients with a negative post-transplant PET/CT compares favorably to that of patients not stratified by PET/CT in prospective trials including a 5-year PFS of 44% in the NLG-T-01 study which looked at 115 PTCL patients who underwent ASCT in the up-front setting (d'Amore F, et al. J Clin Oncol. 2012 Sep 1;30(25):3093-9). Our findings that negative pre-transplant PET/CT are not predictive of survival or associated with an improved 3-year PFS in comparison to positive pre-transplant PET/CT was in keeping with the findings of another retrospective analysis of 48 patients, which compared the 3-year PFS and OS of patients with positive and negative pre-transplant PET/CT studies (Shea L, et al. Leuk Lymphoma. 2015 January; 56(1): 256-259). Disclosures Jacobsen: Merck: Consultancy; Seattle Genetics: Consultancy.

Chronic Myelomonocytic Leukemia and Related Disorders Provide Particular Disease-Specific Challenges to Effective Bone Marrow Transplant: a Multicenter Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4561-4561
Author(s):  
Steven E. McCormack ◽  
Yan Zhang ◽  
Ramon V. Tiu ◽  
Jaroslaw P Maciejewski ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Sibling Donor ◽  
Md Anderson ◽  
Myelomonocytic Leukemia ◽  
Donor Source

Abstract Abstract 4561 Chronic myelomonocytic leukemia (CMML) typically has a dire prognosis with limited treatment options. We retrospectively reviewed the outcomes of 41 patients diagnosed with CMML (n= 35) or MDS/MPD overlap (n=6) who underwent allogeneic stem cell transplantation at three centers (University of Minnesota (n= 19), Johns Hopkins University (n=11), and the Cleveland Clinic (n=11)) between1990-2009. The majority of patients were male (59%) with a mean age of 51. At diagnosis nearly half of the patients had normal cytogenetics (n=20, 49%) with abnormalities of chromosome 7 the most commonly identified clonal finding (n=5, 12%). The majority had <5% blasts (n=22, 54%), and the majority had an MD Anderson Prognostic Score (MDAPS) of 2 (n=16, 39%) or 3 (n=13, 32%) at diagnosis. Fifteen patients (37%) received no pre-transplant therapy while 12 (29%) received hydroxyurea, 11 (27%) induction-type chemotherapy, and 3 (7%) miscellaneous other therapies. Nine patients (22%) had progressed to AML prior to transplant. At the time of transplant, blast percentage was <5% in the majority (n=23, 56%) of patients and more than half of patients now had a MDAPS of 1 (n=13, 32%) or 2 (n=12, 32%). Comorbidity index (HCT-CI) at transplant was retrospectively calculated on 32 patients and was 0 (n=5, 12%), 1–2 (n=13, 32%), or 3+ (n= 15, 37%). Myeloablative conditioning was used in 23 (56%) and stem cell source was bone marrow in 14 (34%), PBSC in 16 (39%), and UCB in 9 (22%). The majority of donors were matched siblings (n=22, 54%) while unrelated donors (URD) (n=16, 39%) and haploidentical donors (n=3, 7%) comprised the remaining. Graft versus host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate or mycophenolate mofetil (MMF) in the majority of patients (n=29, 71%) with the remainder receiving post-transplant cyclophosphamide (n=6, 15%), elutriation (n=2, 5%), or calcineurin inhibitor alone (n=4, 10%). While the median time to follow-up was only 5.8 months (range 0.5–140), 24 patients had died by one year and there was extensive follow-up available in the surviving patients. Overall survival (OS) for the entire cohort at 1 and 3 years was 41% (95% CI, 26–56%) and 16% (95% CI, 6–30%), respectively. No disease or transplant factors significantly impacted survival. Progression free survival (PFS) at 1 and 3 years was 29% (95% CI, 16–43%) and 16% (95% CI, 7–29%), respectively. Sibling donor showed improved PFS at both 1 (45%, 95% CI 24–64%), (p=0.027) and 3 (27%, 95% CI 10–46%), (p=0.04) years. Transplant related mortality (TRM) at Day +100 and 1 year was 27% (95% CI, 13–40%) and 41% (95% CI, 26–57%) respectively. Age at transplant, year transplanted, HCT-CI at transplant, conditioning intensity, donor source, transplant site, or presence of acute graft versus host disease (GVHD) did not impact TRM. Relapse at 1 and 3 years was 29% (95% CI, 15–44%) and 40% (95% CI, 23–56%), respectively. High MDAPS at diagnosis and sibling donor source were the only significant factors impacting relapse. At 1 year, those with an MDAPS of 3–4 had a 53% chance of relapse compared with 29% with a score of 0–1 (p=0.05) and those with a sibling donor had a 9% relapse incidence compared with 50% in the URDs and 67% in the haploidentical setting (p=0.003). Interestingly the presence of acute GVHD at Day +100 was not protective against relapse (40% incidence at 1 year in those with aGVHD versus only 19% for those without). Our data suggest that high MD Anderson Prognostic score at diagnosis predicts for high incidence of relapse post allogeneic stem cell transplantation while a sibling donor source improves rates of relapse and progression free survival. Our data highlight the need for improved CMML treatment paradigms. Augmentation of pre and post transplant therapy including maintenance therapy post transplant are possible approaches to improve outcomes and could be considered for prospective trials. Disclosures: No relevant conflicts of interest to declare.

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