Efficacy of naxitamab in patients with refractory/relapse (R/R) high-risk neuroblastoma (HR-NB) by bone/bone marrow (BM) evaluation, potential sites of residual disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10022-10022
Author(s):  
Brian H. Kushner ◽  
Daniel A. Morgenstern ◽  
Karsten Nysom ◽  
Melissa K. Bear ◽  
Karen Tornøe ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Safety Data ◽  
The United States ◽  
Outpatient Setting ◽  
Minor Response ◽  
Overall Response ◽  
Gm Csf ◽  
Prior Therapy ◽  
Meaningful Activity

10022 Background: NB is the most common extracranial solid tumor in children and half of patients present with high-risk disease. Bone and BM are frequent sites of metastatic disease and can serve as a reservoir for residual disease driving relapse. Naxitamab, a GD2-binding monoclonal antibody, was recently approved in the United States in combination with GM-CSF for the treatment of pediatric patients ≥1 year of age and adult patients with R/R HR-NB in the bone/BM who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe outcomes from the registrational Trial 201 (NCT03363373) detailed by bone/BM involvement. Methods: HR-NB patients with primary refractory disease or incomplete response to salvage treatment following relapse or progressive disease (PD) (in both cases including SD, MR and PR) with disease limited to bone and/or BM were eligible. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3 mg/kg/infusion (9 mg/kg/cycle) in combination with GM-CSF at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Response was assessed after Cycle 2 and then every 2-3 months by revised International Neuroblastoma Response Criteria (INRC) using BM biopsies/aspirates and 123I-MIBG scintigraphy or FDG-PET. Effectiveness was concluded if the lower limit of the Clopper-Pearson exact 95% confidence interval (CI) of overall response rate (ORR) was >20%. We report efficacy data on 22 patients and safety data on the first 25 patients enrolled. Results: 13 (59%) patients had NB in bone, 2 (9%) had NB in BM, and 7 (32%) had NB in both bone and BM. Summary of overall response and response by compartment. Conclusions: Naxitamab provided clinically meaningful activity in both bone and BM with ORR of 68% and had a manageable AE profile. Clinical trial information: NCT03363373. [Table: see text]

Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific Immune Responses After High-Dose Chemotherapy

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 673-683 ◽  
Author(s):  
Massimo Massaia ◽  
Paolo Borrione ◽  
Silvano Battaglio ◽  
Sara Mariani ◽  
Eloise Beggiato ◽  
...  
Keyword(s):  
Immune Responses ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Keyhole Limpet Hemocyanin ◽  
High Dose Chemotherapy ◽  
Outpatient Setting ◽  
Delayed Type Hypersensitivity ◽  
High Dose ◽  
Gm Csf ◽  
Macrophage Colony

Abstract Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.

Azacitidine Plus Gemtuzumab Ozogamicin (GO): A Novel Combination in the Treatment of Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS) in the Elderly.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1981-1981 ◽  
Author(s):  
Sucha Nand ◽  
John Godwin ◽  
Scott Smith ◽  
Kevin Barton ◽  
Eliza Germano ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Residual Disease ◽  
The Elderly ◽  
Gemtuzumab Ozogamicin ◽  
Outpatient Setting ◽  
Grade 3 ◽  
Wbc Count ◽  
Related Mortality

Abstract AML and high-risk MDS in the elderly carry a poor prognosis. Only 46% of AML patients receiving standard chemotherapy achieve complete remission (CR) and treatment-related mortality approaches 30% above age 60. In 2005, we initiated a Phase II trial for elderly patients with newly diagnosed AML or MDS, using the following outpatient treatment schema: If white blood cell (WBC) count at presentation was >10,000/ul, pt was started on hydroxyurea 1500 mg twice daily by mouth. Leukapheresis was performed if WBC >100,000/ul. Once WBC count was <10,000/ul, the patient received azacitidine 75 mg/m2 s/cu D1–7 and GO 3 mg/m2 on D8. A bone marrow was performed on D14 and induction therapy repeated for residual disease. Those who achieved CR were given one consolidation treatment with azacitidine+GO in same doses after recovery of blood counts. A total of 13 pts have been treated to date. Eleven had AML by WHO classification and 2 MDS (both RAEB). The median age was 77 (62–83) and 7 were male. Ten patients required retreatment on D14. Ten patients (76%) achieved CR. Six patients developed grade 3 toxicities: 5 neutropenic fever and 1 typhlitis, all requiring hospitalization. There were no treatment-related deaths. Median follow up is 7 months (2–13 months) and eleven patients remain alive. Two patients have died from relapsed or refractory disease. Nine patients remain in CR with a median duration of remission of 7 months (2–13 months). The trial is ongoing with an accrual goal of 20. Our early experience with this novel combination is quite encouraging. Cytoreduction with hydroxyurea and leukapheresis followed by azacitidine and GO appears to be a safe and effective regimen for elderly patients with AML and the therapy can be given in the outpatient setting. These preliminary results need to be confirmed in a larger cohort of patients.

Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10543-10543
Author(s):  
Jaume Mora ◽  
Godfrey Chi-Fung Chan ◽  
Daniel A. Morgenstern ◽  
Karsten Nysom ◽  
Melissa K Bear ◽  
...  
Keyword(s):  
High Risk ◽  
Objective Response ◽  
High Risk Patient ◽  
Complete Response ◽  
Outpatient Setting ◽  
Response To Therapy ◽  
Gm Csf ◽  
Insufficient Response ◽  
Macrophage Colony ◽  
Relapsed Disease

10543 Background: NB is a rare cancer but represents the most common extracranial solid tumor of childhood. Most HR-NB patients present with or develop metastatic disease typically in bone or bone marrow (BM). Despite advances in frontline multimodal therapy ~50% of patients relapse. Refractory or relapsed disease represents an unmet medical need. GD2 is an adhesion molecule abundantly expressed in NB. Naxitamab is a humanized anti-GD2 mAb with high receptor affinity. Methods: We evaluated naxitamab in HR-NB patients with disease in bone and/or BM, who were refractory to initial treatment(s) or who had insufficient response to therapy for progressive/relapsed disease. Patients were treated in an outpatient setting with naxitamab as a planned 30-minute i.v. infusion and s.c. granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients received 3 infusions of naxitamab 3 mg/kg/dose during the first week of a treatment cycle repeated initially every 4 weeks. Patients were evaluated for safety (CTCAE V4.0) and efficacy (INRC, Park et al. 2017). Results: We report on 24 patients recruited from April 2018 with a data cut off in June 2019. At diagnosis, 21 patients were stage 4, 1 was stage 3, 2 were unknown. At study entry, 11 patients had metastases in bone, 1 in BM and 12 in both bone and BM. Overall objective response was 75% (18/24), with complete response (CR) in 67% (16/24) and partial response in 8% (2/24). Of the 13 patients with BM involvement at enrollment, 12 achieved CR in BM during trial therapy. 6 treatment-related SAEs were reported in 5 patients (anaphylactic reaction, pyrexia, and respiratory depression). Conclusions: Naxitamab is an anti-GD2 mAb under development for HR-NB. In addition to a high CR rate of 67% and an overall objective response rate of 75% in a high-risk patient population, naxitamab offers an unique option for treatment of patients in the outpatient setting. These data and convenience to patients are strongly supportive of further drug development. Clinical trial information: NCT03363373.

Response to Bortezomib Therapy for Multiple Myeloma (MM) in Actual Clinical Practice: Preliminary Effectiveness Findings of an International Observational Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4837-4837
Author(s):  
Michel Delforge ◽  
Eirini Katodritou ◽  
Konstantinos Zervas ◽  
Deniz Sargin ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Safety Data ◽  
Response Rates ◽  
Complete Response ◽  
Response Criteria ◽  
Actual Clinical Practice ◽  
Overall Response ◽  
Prior Therapy ◽  
Best Response

Abstract Background: Bortezomib (VELCADE®) is indicated for the treatment of MM in patients (pts) who have received at least 1 prior therapy. The electronic VELCADE Observational Study (eVOBS) is designed to evaluate the clinical and outcomes benefits of bortezomib in actual clinical practice. The study is open for enrollment between October 2006 and December 2008 in Belgium, France, Greece, Russia, Spain, Sweden, and Turkey with 3-year follow up. This report includes preliminary outcomes in pts with at least 4 months of data as of July 2007. Methods: Adults were eligible for study if they were scheduled to initiate bortezomib within the approved indication. All bortezomib dosages and concomitant treatments were permitted, except investigational therapies. Data on concomitant therapies, treatment response, and safety were collected prospectively during bortezomib therapy. Due to the non-interventional nature of the study, no predefined response criteria were mandated; response criteria could include M-protein, EBMT, SWOG, or others as defined by the investigator. Results: A total of 86 pts with at least 4 months of data were included in this analysis. Median age was 61 yrs, and 50 (58%) pts were male. Median interval since diagnosis was 3 yrs. The number of previous therapies for MM was 1, 2–3, and ≥4 for 38%, 44%, and 11% of pts, respectively. Demographic and clinical characteristics of the initial participants were similar to those of the participants in the prospective controlled phase 3 APEX trial (Richardson, N Engl J Med, 2005:352; 2487–98). Most pts (61%) received bortezomib with dexamethasone. Adverse events (AEs) were reported in 61 (71%) pts, including Grade ≥3 AEs in 38% and Grade ≥4 AEs in 9%. AEs were treatment-related in 45% of patients and treatment-limiting in 9%. Presently, 72 of 86 pts have been evaluated for response, of whom 54 completed 4 or more cycles. Response rates are shown in the table. Updated data will be presented at the meeting. Best Response(n = 72) Complete response (CR) 5 (7) Near complete response (nCR) 9 (13) Partial response (PR) 30 (42) Minimal response (MR) 9 (13) Stable disease (SD) 6 (8) Progressive disease (PD) 13 (18) Overall response (≥PR) 44 (61) Overall response (≥MR) 53 (74) Conclusions: In this preliminary analysis of data from a prospective, observational study of actual clinical practice, most pts received bortezomib in combination with 1 or more other therapies for MM. Overall response in actual clinical practice was at least as common as previously reported with bortezomib monotherapy. Response rates and safety data from actual clinical practice demonstrate that bortezomib-containing regimens are effective and well-tolerated in the treatment of MM.

Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific Immune Responses After High-Dose Chemotherapy

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 673-683 ◽  
Author(s):  
Massimo Massaia ◽  
Paolo Borrione ◽  
Silvano Battaglio ◽  
Sara Mariani ◽  
Eloise Beggiato ◽  
...  
Keyword(s):  
Immune Responses ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Keyhole Limpet Hemocyanin ◽  
High Dose Chemotherapy ◽  
Outpatient Setting ◽  
Delayed Type Hypersensitivity ◽  
High Dose ◽  
Gm Csf ◽  
Macrophage Colony

Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.

Phase II study of oxaliplatin, docetaxel, and sargramostim (GM-CSF) in patients with previously treated advanced melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8570-8570
Author(s):  
F. L. Locke ◽  
J. I. Clark ◽  
T. F. Gajewski
Keyword(s):  
Advanced Melanoma ◽  
Prior Treatment ◽  
Clinical Activity ◽  
Minor Response ◽  
Gm Csf ◽  
Prior Therapy ◽  
Treatment Regimens ◽  
Treatment Naïve ◽  
Previously Treated ◽  
A Minor

8570 Background: Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. Methods: Eligibility included intact organ function, PS=2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes, and no chremophor allergy. After premedication, docetaxel was administered day 1 at 85 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (5 μg/kg) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every 2 cycles by RECIST criteria. Results: 20 patients were enrolled, 13 with 1 prior therapy, 5 with 2 prior therapies, and 2 previously untreated. Six patients did not complete 2 cycles and were not formally evaluable for response. One patient who failed 2 prior treatment regimens experienced a minor response and received 10 cycles of therapy, and 4 patients had stable disease. The rest showed PD after 2 cycles. Notable toxicities included 7 cases of grade III/IV neutropenia and 2 hypersensitivity reactions. Conclusions: This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naive patients may still be warranted. No significant financial relationships to disclose.

Daratumumab, lenalidomide, and dexamethasone (DRd) vs lenalidomide and dexamethasone (Rd) in relapsed or refractory multiple myeloma (RRMM): Efficacy and safety update (POLLUX).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8025-8025 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Philippe Moreau ◽  
Hareth Nahi ◽  
Torben Plesner ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Residual Disease ◽  
Safety Data ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Prior Therapy ◽  
Line Of Therapy ◽  
Favorable Safety

8025 Background: Daratumumab (D) is a human CD38-targeting mAb that significantly prolongs progression-free survival (PFS) when added to standard-of-care regimens in patients (pts) with RRMM. We examined updated efficacy and safety data from POLLUX (NCT02076009), a randomized phase 3 study of DRd vs Rd in RRMM. Methods: Pts with ≥1 prior line of therapy (LOT) received Rd (25 mg PO lenalidomide on days 1-21 of each q4w cycle; 40 mg dexamethasone weekly) ± D (16 mg/kg IV qw for cycles 1 and 2, q2w for cycles 3-6, then q4w until disease progression). Pts refractory to lenalidomide were ineligible. Minimal residual disease (MRD) was assessed on bone marrow samples at time of suspected complete response (CR) and at 3 and 6 months post-suspected CR at sensitivities of 10–4, 10–5, and 10–6 via next-generation sequencing (Adaptive Biotechnologies, Seattle, WA). Results: Pts received a median (range) of 1 (1-11) prior LOT. 55% received prior IMiDs (18% lenalidomide). Based on previous median follow-up of 17.3 months, DRd significantly prolonged PFS (median: not reached vs 17.5 months; HR, 0.37; 95% CI, 0.28-0.50; P< 0.0001) and significantly improved overall response rate (ORR; 93% vs 76%, P< 0.0001) vs Rd. DRd induced higher rates of deep responses vs Rd (≥very good partial response [VGPR]: 78% vs 45%; ≥CR: 46% vs 20%; all P< 0.0001) and included MRD negativity, which was > 3-fold higher across all 3 sensitivity thresholds for DRd vs Rd (25% vs 6% at the 10–5 threshold). MRD-negative pts demonstrated longer PFS vs MRD-positive pts. Follow up for overall survival (OS) is ongoing (OS events: 40 [14%] in DRd and 56 [20%] in Rd). No new safety signals were identified with longer follow up. Updated efficacy and safety data based on approximately 25-months follow up will be presented at the meeting. Conclusions: DRd provided significant benefits vs Rd in terms of PFS, ORR, and MRD negativity, and the favorable safety profile of DRd was maintained with longer follow up. These data further validate the use of DRd in RRMM pts who received ≥1 prior therapy. Clinical trial information: NCT02076009.

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