scholarly journals Prospective SPECT-CT Organ Dosimetry-Driven Radiation-Absorbed Dose Escalation Using the In-111 (111In)/Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Theranostic Pair in Patients with Lymphoma at Myeloablative Dose Levels

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2828
Author(s):  
Richard L. Wahl ◽  
Eric C. Frey ◽  
Heather A. Jacene ◽  
Brad S. Kahl ◽  
Steven Piantadosi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Dose Escalation ◽  
Tumor Response ◽  
Absorbed Dose ◽  
Patient Specific ◽  
Cell Transplant ◽  
Ibritumomab Tiuxetan ◽  
Anti Cd20 ◽  
Dose Levels ◽  
Stem Cell Collection

Purpose: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin’s lymphoma using the theranostic pair of 111In and 90Y anti-CD20 ibritumomab tiuxetan (Zevalin®) at myeloablative radiation-absorbed doses with autologous stem cell support. We also assessed acute non-hematopoietic toxicity and early tumor response in this two-center outpatient study. Methods: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts > 75,000/mm3, and <35% tumor involvement in the marrow were treated with Rituximab (375 mg/m2) weekly for 4 consecutive weeks, then one dose of cyclophosphamide 2.5 g/m2 with filgrastim 10 mcg/kg/day until stem cell collection. Of these, 18 patients with successful stem cell collection (at least 2 × 106 CD34 cells/kg) proceeded to RIT. A dosimetric administration of 111In ibritumomab tiuxetan (185 MBq) followed by five sequential quantitative planar and one SPECT/CT scan was used to determine predicted organ radiation-absorbed dose. Two weeks later, 90Y ibritumomab tiuxetan was administered in an outpatient setting at a cohort- and patient-specific predicted organ radiation-absorbed dose guided by a Continuous Response Assessment (CRM) methodology with the following cohorts for dose escalation: 14.8 MBq/kg, and targeted 18, 24, 28, and 30.5 Gy to the liver. Autologous stem cell infusion occurred when the estimated marrow radiation-absorbed dose rate was predicted to be <1 cGy/h. Feasibility, short-term toxicities, and tumor response were assessed. Results: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of 90Y (range: 12.1–41.4 MBq/kg)) of ibritumomab tiuxetan that was required to deliver 10 Gy to the liver. Infused stem cells engrafted rapidly. The most common treatment-related toxicities were hematological and were reversible following stem cell infusion. No significant hepatotoxicity was seen. One patient died from probable treatment-related causes—pneumonia at day 27 post-transplant. One patient at dose level 18 Gy developed myelodysplastic syndrome (MDS), 4 patients required admission post-90Y RIT for febrile neutropenia, 16/18 patients receiving 90Y ibritumomab tiuxetan (89%) responded to the therapy, with 13 CR (72%) and 3/18 PR (17%), at 60 days post-treatment. Two patients had progressive disease at sixty days. One patient was lost to follow-up. Median time to progression was estimated to be at least 13 months. MTD to the liver is greater than 28 Gy, but the MTD was not reached as the study was terminated due to unexpected discontinuation of availability of the therapeutic agent. Conclusions: Patient-specific outpatient 90Y ibritumomab tiuxetan RIT with myeloablative doses of RIT up to a targeted 30.5 Gy to the liver is feasible, guided by prospective SPECT/CT + planar imaging with the theranostic pair of 111In and 90Y anti-CD20, with outpatient autologous stem cell transplant support. Administered activity over 5 times the standard FDA-approved activity was well-tolerated. The non-hematopoietic MTD in this study exceeds 28 Gy to the liver. Initial tumor responses were common at all dose levels. This study supports the feasibility of organ dosimetry-driven patient-specific dose escalation in the treatment of NHL with stem cell transplant and provides additional information on the radiation tolerance of the normal liver to radiopharmaceutical therapy.

Dose finding trial of Yttrium 90 ibritumomab tiuxetan (90YIT) with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7535-7535 ◽  
Author(s):  
I. W. Flinn ◽  
B. S. Kahl ◽  
E. C. Frey ◽  
J. A. Bianco ◽  
R. J. Hammes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Dose Escalation ◽  
Bone Marrow Involvement ◽  
Absorbed Dose ◽  
Hepatic Function ◽  
Maximum Tolerated Dose ◽  
Outpatient Setting ◽  
Dose Finding ◽  
Ibritumomab Tiuxetan ◽  
Post Transplant

7535 Background: 90YIT is an effective agent for patients with lymphoma. Unfortunately, dose escalation is limited by hematopoetic toxicity. In order to determine the non-hematopoetic maximum tolerated dose, we are conducting a dose finding study of 90YITwith ASCT. Methods: Eligible patients had relapsed or refractory NHL, rituximab sensitive disease, age ≥18 years, platelet count ≥75,000/mm3, WBC >3,000/mm3, bone marrow involvement ≤35%, and acceptable renal and hepatic function. Patients receive weekly rituximab (375 mg/m2) for 4 consecutive weeks followed by a single dose of cyclophosphamide (2.5 g/m2). Filgrastim 10 mcg/kg is administered post cyclophosphamide until stem cell collection. Following successful collection of at least 2 X 106 CD34/kg, patients receive a dosimetric dose of indium 111 (111In) ibritumomab tiuxetan (5 mCi) on day 1, quantitative planar and SPECT/CT scans followed by cohort specific dose of 90Y IT on day 15. Stem cell infusion occurs when estimated marrow dose rate is < 1 cGy/hour. Results: 22 patients (12M:10F) (median age 55, 44–70) with a median of 2 prior regimens (range, 1–8) have been entered onto study. 5 patients failed to mobilize stem cells and did not receive 90YIT. 16 patients have been treated with 90Y IT to the following dose cohorts based on dosimetry-predicted maximal organ radiation absorbed dose: 0.4 mCi/kg = 3; 14–18 Gy = 5; 24 Gy = 6, 28 Gy = 2. The range of administered 90Y IT activities was 20.2–143.1 mCi. All patients engrafted rapidly. One patient died from treatment-related causes: pneumonia day 27 post-transplant. At 60 days post-transplant, 10 patients achieved a CR, 3 patients had a PR, and 2 had progressive disease. The most common treatment-related toxicities were hematologic, as expected. This therapy was delivered completely in the outpatient setting. 4 patients required admission post 90YIT for febrile neutropenia. No significant hepatotoxicity has been seen to date despite the fact that the liver is the organ that receives the highest absorbed dose of radiation. Conclusions: Significant dose escalation with 90YIT can be achieved with ASCT. Dose escalation continues and the MTD has yet to be determined. [Table: see text]

scholarly journals Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4848-4848
Author(s):  
Brad Rybinski ◽  
Ashraf Z. Badros ◽  
Aaron P. Rapoport ◽  
Mehmet Hakan Kocoglu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Number Of Cycles ◽  
Time Required ◽  
Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

scholarly journals Study of Peripheral Mononuclear Cells and CD34 Levels as a Predictive Marker for Initiating Apheresis in Autologous Stem Cell Transplant

2021 ◽  
Author(s):  
Kiran PK ◽  
Vinu Sarathy P ◽  
Srinivas BJ ◽  
Girish V Badarkhe ◽  
Rajesh Kumar KS ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Cell Count ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Optimal Time ◽  
Cell Transplant ◽  
Stem Cell Collection

Background: Autologous HCT in multiple myeloma is done as upfront treatment in newly diagnosed transplant eligible patients after induction chemotherapy. In addition, it is standard for relapsed, aggressive non-Hodgkin lymphoma (NHL) and classical Hodgkin lymphoma (HL), and is curative in ~40% to 45% of patients. Over a decade, many efforts were made to find helpful parameters to predict an optimal time for initiating an efficient peripheral blood stem cell collection so that adequate stem cells are collected.  It has been well accepted that CD34+ cell count in peripheral blood before leukapheresis is the best parameter to predict CD34 cell yield. However, white blood cell count, mononuclear cell count, and other easily obtained parameters are still used to guide the clinical practice of peripheral blood stem cell mobilization and collection.  Materials and Methods: In the present study, we analyzed the correlation between peripheral blood MNC and Apheresis CD34 levels and also between peripheral blood CD34 by flow cytometry and apheresis CD34 levels. Results: We found that there was a statistically insignificant weak correlation between peripheral MNC and apheresis CD34. There was a statistically significant strong correlation between peripheral CD34 and apheresis CD34. Conclusion: The results show that peripheral blood MNC was analogous indicating that no reliable prediction can be done for CD34 cells collected in apheresis while peripheral CD34 by flow cytometry is the strongest predictor for initiating stem cell collection.

Targeted Radiotherapy in the Conditioning Prior to Haematopoietic Stem Cell Transplantation: Results of a Phase I Radiation Dose Escalation Study Using Yttrium-90-Labelled Anti-CD66 Monoclonal Antibody Demonstrating High BM Uptake of Radiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2189-2189
Author(s):  
Kim Orchard ◽  
Margaret Cooper ◽  
Valerie Lewington ◽  
Maria Tristram ◽  
Maureen Zivanovic ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Stem Cell ◽  
Radiation Dose ◽  
Dose Escalation ◽  
Radiation Doses ◽  
Dose Escalation Study ◽  
Dose Levels ◽  
Reduced Intensity ◽  
Yttrium 90

Abstract We report the results of a phase I clinical study using a radiolabelled murine anti-CD66 IgG1 monoclonal antibody (TheraPharm GmbH) as part of the transplant conditioning schedule for patients receiving either autologous or allogeneic stem cell transplants (SCT) for myeloma or acute myeloid leukaemia. This was a radiation dose escalation study using increasing doses of yttrium-90 (Y-90) as the therapeutic radionuclide. A total of eighteen patients have been treated over four Y-90 radiation dose levels. All patients received an initial infusion of indium-111 (In-111)-labelled anti-CD66 for biodistribution and dosimetry determination. If favourable dosimetry was demonstrated, patients went on to receive the therapy dose of radiation, the dose of Y-90 infused calculated from the patient’s body weight. The Y-90 dose levels were as follows: 5, 10, 25 and 37.5MBq /kilogram (lean) body weight. Patient characteristics: Age 21-67 yrs (median 54 yrs); 14 male, 4 female; myeloma 14, AML 4; autologous SCT 14, reduced intensity allogeneic SCT 4. Patients undergoing autologous SCT for myeloma received Y-90 labelled anti-CD66 on day -14 and melphalan 200mg/m2 on day -2. Patients undergoing reduced intensity allogeneic SCT received Y-90-labelled anti-CD66 on day -14 in addition to a reduced intensity schedule of fludarabine, melphalan and CAMPATH 1H. Results: Excellent bone marrow targeting was seen in all patients and in the majority low uptake by non-haematopoietic organs, in particular liver uptake was consistently low. There was a close correlation between the administered dose of Y-90 and the dose delivered to the bone marrow but not for the radiation dose received by the liver. Mean absorbed radiation doses (cGy per MBq infused Y-90): bone marrow 10.23 +/- 1.8 cGy/MBq; liver 2.67 +/- 2.0 cGy/MBq; spleen 7.10 +/- 3.75 cGy/MBq. Total absorbed radiation doses at each dose level are in table 1. Table 1 Organ dose in Gy Dose level MBq per kg BM Liver Spleen 5 4.1 1.4 1.1 10 9.1 1.3 2.4 25 15.6 3.7 12.6 37.5 22.0 7.8 5.3 No additional toxicity due to the addition of targeted radiation was seen. Engraftment: neutrophils >0.5 by day + 13.8 (11-22) platelets >50 day +12.7 (10-22), no graft failures were seen. In two patients with myeloma, focal uptake of In-111-labelled antibody was seen suggesting in vivo targeting of myeloma, consistent with the expression of the antigen on plasma cells demonstrated by Flow cytometry. Conclusions: The anti-CD66 monoclonal antibody showed consistently excellent BM targeting and very low uptake by non-haematopoietic organs. Up to 25 Gy of additional radiation was delivered to the bone marrow with no additional toxicity. This particular monoclonal antibody may have a role in stem cell transplantation for a wide range of haematological malignancies, providing significant dose escalation without toxicity in autologous and allogeneic protocols. AntiCD66 may be particularly appropriate in transplantation for myeloma.

Outcomes Following Autologous Stem Cell Transplantation (ASCT) In Patients With Germinal Center B (GCB) and Non-GCB Cell-Like Diffuse Large B Cell Lymphomas (DLBCL) According To Conditioning With BEAM-Rituximab (Standard vs. High-Dose) Vs. BEAM/Yttrium-90 Ibritumomab Tiuxetan (90YIT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3350-3350
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Zijun Y Xu-Monette ◽  
Gabriela Rondon ◽  
Rosamar Valverde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Of Origin ◽  
Ibritumomab Tiuxetan ◽  
Bone Marrow Biopsies ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
The Impact

Abstract Background Patients with a DLBCL of GCB immunophenotype have a higher chance of cure than patients with non-GCB DLBCL when treated with conventional chemotherapy. In the relapsed/refractory setting, there are conflicting data regarding the impact of cell-of-origin classification on survival following ASCT. The addition of high-dose rituximab (HDR) (1000 mg /m2 days +1 and +8 after ASCT) has been shown to improve results for patients with relapsed DLBCL who undergo transplantation (Khouri et al, J Clin Oncol 2005;23:2240-7). The optimal rituximab dose to be used with ASCT [HDR vs. standard dose (SDR) 375 mg/m2 days +1 and +8)] has been under investigation at our center. More recently, we and others reported on the safety of incorporating 90YIT (0.4 mCi/Kg) in the conditioning. Herein, we compare outcomes of patients with GCB and non-GCB DLBCL after ASCT according to the conditioning regimen received. Methods and patients 121 de novo DLBCL patients were treated on 4 consecutive trials between 2000 and 2012. We determined the cell-of-origin, based upon the Visco/Young and Choi immunohistochemical algorithms, and classified 64 (53%) as GCB and 57 (47%) as non-GCB tumors. Median age, gender distribution, remission status (CR vs PR), # of prior therapies, IPI, beta-2 microglobulin and LDH distribution were similar in both groups. Patients were staged with CT, PET (whenever indicated) scans and bone marrow biopsies, every 3 months for the first year, every 6 months x 5 years, then yearly thereafter. Patients received BEAM conditioning with either SDR [GCB (n =14), non-GCB (n=7), HDR [GCB (n =31), non-GCB (n=40) or 90YIT[GCB (n =19), non-GCB (n=10)]. Results Determinants for progression (cell-of-origin, age, and gender, and disease status, # of prior therapies, IPI, beta-2 microglobulin and LDH distribution) were studied within each type of conditioning. Within the BEAM-SDR group, the cell-of-origin was the only significant predictor for relapse at 3-years (86% in non-GCB vs. 14% in GCB; P=0.01) (Figure), resulting in improved OS and PFS for the GCB group (both 71% vs 14%, respectively, P=0.06 for OS and 0.04 for PFS). Non-relapse mortality was 0% in this group. Within the BEAM-HDR and BEAM-90YIT groups, GCB and non-GCB patients had a similar rate of relapse (30% vs. 38%, respectively at 3-year, P=0.4) and similar 3-year PFS rates 66% vs 56%, P=0.3), and 3-year OS of 77% vs. 61% (P=0.09). Conclusion Our results suggest similar outcomes for patients with DLBCL of GCB and non-GCB immunophenotype when either HDR or 90YIT is added to the BEAM conditioning. A SDR has been found to be associated with a significantly higher risk of progression and inferior survival in non-GCB patients. Disclosures: Khouri: Spectrum Pharmaceuticals: Consultancy, Research Funding. Off Label Use: Rituximab and ibritumomab tiuxetan for stem cell transplant.

A Phase I Study Of Myeloablative Radioimmunotherapy Using Iodine-131 Anti-CD45 Antibody Followed By Autologous Stem Cell Transplantation For High-Risk B-Cell and T-Cell Non-Hodgkin Lymphoma and Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3333-3333 ◽  
Author(s):  
Ryan D. Cassaday ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
Joseph G. Rajendran ◽  
Theodore A. Gooley ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Phase I ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Escalation ◽  
Absorbed Dose ◽  
High Dose ◽  
Normal Organ

Abstract Background High-dose therapy and autologous stem cell transplant (ASCT) remains the standard of care for many high-risk/relapsed B-cell non-Hodgkin lymphomas (B-NHL), T-cell NHL (T-NHL) and classical Hodgkin lymphoma (HL), yet most will not achieve sustained remissions. High-dose anti-CD20 radioimmunotherapy (RIT) and ASCT has been successfully employed to address this challenge in B-NHL, yet relapse still occurs potentially due to blockade of target sites by circulating rituximab (R). RIT options are limited for patients with T-NHL and HL. Preclinical data indicate that targeting the panhematopoietic antigen CD45 with RIT can successfully circumvent R blocking in B-NHL and target a variety of T-NHL histologies (Gopal, 2008 & 2009). We thus performed a phase I trial using high-dose anti-CD45 RIT and ASCT for B-NHL, T-NHL, and HL. Methods Patients were ≥18 years old with relapsed, refractory, or high-risk B-NHL, T-NHL, or HL and had acceptable organ function with an ECOG performance status of 0-1 and no detectible human anti-mouse antibodies. They could not have received ≥20 Gy of prior radiation (RT) to critical organs or prior ASCT within 1 year, or prior allogeneic transplant at any time. All patients first received anti-CD45 antibody (BC8) trace-labeled with 131I followed by gamma camera imaging to evaluate biodistribution and estimate organ-specific absorbed doses. Patients then received 131I-BC8 at an absorbed dose determined by the following: Patients with prior RT >20 Gy or prior ASCT started at 10 Gy to the dose-limiting normal organ (Arm A), while others started dose escalation at 20 Gy (Arm B). Subsequent dose escalation/de-escalation followed a two-stage approach (Storer, 2001). ASCT occurred after sufficient radiation decay, and G-CSF was started on day 1. Dose limiting toxicity (DLT) was determined by Bearman grade III/IV events. The primary objective was to estimate the maximum tolerated dose, defined as that yielding a DLT rate of 25%. Responses were scored using standard criteria (Cheson, 2007). Results Between August 2009 and March 2013, 15 patients were treated. Median age was 62 years (range 20-71); stage III/IV = 11 (73%); median prior regimens = 3 (range 2-12), including 1 prior ASCT; chemorefractory disease (i.e., <PR to the most recent chemotherapy) = 8 (53%); histologies were HL (n = 6), B-NHL (n = 6), and T-NHL (n = 3; see Table). The mean administered 131I activity was 646 mCi (range 344-1064 mCi; 23.9 GBq, range 12.7-39.4 GBq). The liver was the dose-limiting normal organ in 12 patients (2.41-3.98 cGy/mCi). The absorbed dose was escalated to 14 Gy for patients in Arm A (n = 3) and 30 Gy in Arm B (n = 12). Neutrophil (>500/μl) and platelet (>20 K/μl) engraftment occurred a median of 8 (range 10-20) and 12 (range 8-26) days after ASCT, respectively. No DLTs, non-relapse deaths, or non-hematologic toxicities > NCI-CTCAE v3 grade 3 have been observed. Currently, 11 (73%) patients are alive and 7 (47%) are progression-free with a median follow-up of 12 months. Seven (54%) of 13 patients with measurable disease at enrollment had objective disease responses, including 3 of 3 with T-NHL, 3 of 6 with HL, and 1 of 1 with follicular lymphoma (FL; see Table). Conclusion Myeloablative doses of 131I targeted to CD45 are safe and feasible in patients with lymphoma, with no DLTs observed after delivery of up to 30 Gy to the liver. Objective disease responses in heavily-treated B-NHL, T-NHL, and HL were observed. This work has led to current studies using yttrium-90 as the therapeutic radionuclide (given its longer beta pathlength and absence of gamma emission) in anti-CD45 RIT for lymphoma. Disclosures: No relevant conflicts of interest to declare.

PX-171–006: Phase Ib multicenter dose escalation study of carfilzomib (CFZ) plus lenalidomide (LEN) and low-dose dexamethasone (loDex) in relapsed and refractory multiple myeloma (MM): Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8541-8541
Author(s):  
R. Niesvizky ◽  
W. Bensinger ◽  
M. Vallone ◽  
A. Gutierrez ◽  
L. Kunkel
Keyword(s):  
Dose Escalation ◽  
Low Dose ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Cell Transplant ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Dose Levels ◽  
Dose Limiting Toxicity

8541 Background: CFZ is a highly specific proteasome inhibitor with single agent activity in relapsed/refractory MM (ASH 2008). The purpose of this study is to evaluate the safety and activity of CFZ in combination with LEN and loDex. Methods: This phase Ib trial evaluates 4 dose levels (≥ 3 pts each) to define the maximum tolerated dose (MTD) of CFZ/LEN/loDex in relapsed/refractory MM pts who failed 1–3 prior therapies, including prior LEN or bortezomib (BTZ). CFZ IV 15- 20 mg/m2 (d1,2,8,9,15,16), LEN 10–20 mg po (d1–21) and loDex 40 mg po (d1, 8, 15, 22) in 28-day cycles (C). An additional 10–15 pts will be evaluated at the highest dose level reached. Dose limiting toxicity (DLT) has been defined as grade (G) ≥ 3 non- hematologic; G4 neutropenia for > 7d and/or neutropenic fever; G4 thrombocytopenia > 7d or G3-G4 thrombocytopenia in association with bleeding. Overall response (CR/sCR, VGPR/PR) is assessed by IWG criteria, with secondary assessment by modified EBMT criteria which includes MR. Results: 11 pts have been enrolled. 8/11 are evaluable for response and toxicity. Median prior lines of therapy was 2 (range 2–3). Prior therapies included DEX (8/8), BTZ (6/8), LEN (7/8), alkylators (6/8), anthracyclines (5/8), stem cell transplant (5/8), and thalidomide (1/8); 6/8 pts had received both LEN and BTZ. MTD has not yet been reached after the first 2 dose cohorts. No drug related SAEs or G3/4 treatment emergent AEs were reported. Responses to date with a median of 2 C (range 1–4) are shown below. Responses were rapid and occurred within the first 28-day cycle. Conclusions: CFZ/LEN/loDex in combination was well tolerated in the first 2 cohorts. There have been no myleosuppressive or renal DLTs. The combination has achieved early encouraging responses in pts who had failed both LEN and BTZ at doses well below the single agent MTD of either LEN or CFZ. Dose escalation is ongoing. Updated data will be presented at the meeting. [Table: see text] [Table: see text]

scholarly journals Utilization of Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma Patients Lacking Geographic Proximity to a Transplant Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4085-4085
Author(s):  
Megan B Sears-Smith ◽  
Lillian Charboneau ◽  
Renju Raj ◽  
R. Eric Heidel
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Systemic Disease ◽  
Age At Diagnosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
First Line ◽  
Transplant Center ◽  
Stem Cell Collection

Abstract Introduction: Autologous stem cell transplant (ASCT) is considered standard of care in young and fit patients with newly diagnosed multiple myeloma. ASCT has shown to improve depth of response, progression free survival and overall survival compared to systemic therapy alone in myeloma patients (Harousseau et al. New England Journal of Medicine). Proximity to a stem cell transplant center may influence the utilization of this therapeutic option in transplant eligible multiple myeloma patients. Our cancer center did not have a stem cell transplant program in the 100-mile driving radius. The goal of this study was to assess the referral patterns and utilization of ASCT in newly diagnosed, young (age &lt;65 years) multiple myeloma patients in a setting where patients are lacking proximity to a transplant center. Methods: The study was an IRB-approved retrospective cohort study. Patients between 18 and 65 years of age at the time of diagnosis who were diagnosed with multiple myeloma between January 1, 2014, and December 31, 2020, were included. Data including age at diagnosis, sex, race, zip code, treatment regimen, clinical data-including referral to a transplant center, stem cell collection and transplant-were collected and analyzed. Staging was calculated using lab values at the time of diagnosis or within 2 weeks of starting treatment. Date of diagnosis was defined as the date of bone marrow biopsy confirming systemic disease. All frequency and descriptive analyses were performed using SPSS Version 26 (Armonk, NY: IBM Corp.) Results: There were n = 62 patients that met the study inclusion criteria. Patients were mainly white (86%) and male (58%) with an average age at diagnosis of 55.9 (SD = 6.83) years. All patients (n = 62, 100%) lived at zip codes that were more than 100 miles from the closest transplant center. ISS staging showed 37% (n = 23, 95% CI 25% - 50%), 29% (n = 18, 95% CI 18% - 42%), and 18% (n = 11, 95% CI 9% - 30%) to have stage I, II, and III disease respectively. Twelve patients (n = 12, 19.4%, 95% CI 10.4% - 31.4%) had insufficient data for staging. The most common first line regimens were bortezomib, lenalidomide, and dexamethasone (n = 39, 62.9%, 95% CI 49.7% - 74.8%) and bortezomib, cyclophosphamide, and dexamethasone (n = 13, 21%, 95% CI 11.7% - 33.2%). Most patients (n = 48, 77.4%, 95% CI 65% - 87.1%) achieved a very good partial response or better. Eight (n = 8, 13%, 95% CI 5.7% - 23.9%) patients had refractory disease to first line therapy. Forty-six (n = 46, 74%, 95% CI 62% - 85%) patients were referred for HSCT evaluation, n = 16 (26%, 95% CI 15.5% - 38.5%) patients were not. Of the forty-six (n = 46) patients that were referred, n = 44 (96%, 95% CI 85% - 99.5%) patients had a clinical consultation with the transplant team. Of the entire cohort, n = 36 (58%, 95% CI 44.9% - 70.5%) patients underwent stem cell collection and n = 34 (55%, 95% CI 42% - 68%) patients underwent an ASCT after induction therapy. Conclusions: Our study found that more than one third of young patients with newly diagnosed multiple myeloma did not undergo stem cell collection or stem cell transplant. Lack of geographic access to a transplant center may be a contributing factor to the under utilization of this highly effective therapeutic strategy. Further investigation into interventions to improve ASCT referral and completion rates is imperative for improving outcomes for patients in such geographic locations. Disclosures Raj: Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz pharmaceuticals: Speakers Bureau; Glaxo-Smith Kline: Speakers Bureau.

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