Leopard: A Phase II Study Of Post Autologous Stem Cell Transplantation (ASCT) Maintenance Lenalidomide and Prednisolone For Myeloma (MM), Incorporating Minimal Residual Disease (MRD) Assessments

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3223-3223
Author(s):  
Anna Kalff ◽  
Nola Kennedy ◽  
Patricia A. Walker ◽  
Marion Black ◽  
Odette Youdell ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Minimal Residual Disease ◽  
Phase Ii ◽  
Residual Disease ◽  
High Dose ◽  
Poor Risk ◽  
Depth Of Response ◽  
Best Response ◽  
Grade 3 ◽  
Minimal Residual

Abstract Background Despite improved outcomes achieved with high dose melphalan conditioned ASCT for MM patients, relapse is inevitable. Consolidation/maintenance therapy with novel agents following ASCT can prolong progression free (PFS) and overall survival (OS) as well as further improve depth of response, the latter being associated with superior survival. More sensitive techniques are now available to monitor minimal residual disease (MRD). Aim To document disease response changes in MM patients receiving maintenance lenalidomide and alternate-day prednisolone (RAP) after a single ASCT. To sequentially quantify MRD in those patients achieving an immunofixation negative (IF-) complete response (CR) utilizing freeLite chain (FLC), hevyLite chain (HLC, in patients with intact IgG or IgA immunoglobulin) and multiparameter flow cytometry (MFC). To assess PFS/OS and safety/tolerability. Methods Phase II, open label, single arm, multi-center study. Newly diagnosed patients with MM were commenced on RAP (lenalidomide 10mg/continuous daily increasing to 15mg after 8 weeks and alternate day prednisolone 50mg) 6-8 weeks after a single MEL200 ASCT as part of first-line therapy. RAP was continued until unacceptable toxicity or relapse/progression. Serum for FLC/HLC was collected every 2 months. Patients achieving an IF- CR had serial BMATs for MFC. This is an interim analysis of the first 30 of a total of 60 patients recruited to the study. Results This analysis included 30 patients (M 17, F 13), median age 61 years (range 46-71), ISS stage I: 11, II/III: 19. 27 patients had diagnostic cytogenetics +/- FISH performed - 10 had poor risk features (t(4;14), t(14;16), del17p, del13 and/or +1q). After a median 549 days (range 385-768), 16 patients remain on therapy. Median PFS was 470 days (range 64-768), median OS was 514 days (range 247-768). Discontinuation was due to relapse/progressive disease in 8, AEs in 5 and poor compliance in 1. 4 patients have died; 3 due to MM and 1 due to therapy related AML [tAML]. The best achieved overall response rate (ORR) was 100%, with 19 IF- CR (63%) (13 stringent CR [sCR]), 10 VGPR (33%) and 1 PR (3%). 16 patients demonstrated an enhanced response while on RAP, including conversion to CR (n=3) or sCR (n=10) (6/10 were MFC negative [MFC-]). Median time to achieving best response was 111 days (range 28-287). 18 patients who achieved IF- CR had MFC studies and 11 were MFC-: of these 11, 5 had normal (FLC-) and 6 abnormal (FLC+) FLC ratios. Five of the 18 were MFC+, 4 of whom were FLC- and have not relapsed. Two of the 18 fluctuated between MFC+ and MFC-. Seven IF- CR patients had HLC analysis; 5/7 patients were MFC- in all samples, 3 of which also had normal HLC ratios (HLC-) and were FLC-. 2/7 patients were MFC+/HLC-. 10 patients relapsed/progressed after a median of 229 days (64-621), 5 from IF- CR (3 sCR). 5/8 with diagnostic cytogenetics had poor risk features, all with +1q in addition to other abnormalities. 3/19 remaining patients with cytogenetics who did not progress have +1q, suggesting a trend (p=0.07) to worse PFS in those with 1q+. In those who relapsed from IF- CR: 2 converted from MFC- to MFC+ prior to relapse/HLC-, 1 was FLC+ and 1 converted to FLC+ at relapse; 2 were MFC-/FLC- converting to FLC+ at relapse; 1 was MFC+/FLC+). All grade haematologic AEs comprised thrombocytopenia 7/30 (23%) (grade 3/4: 4), neutropenia 2/30 (grade 3: 1) and anaemia 3/30(grade 3: 1). All grade non-haematologic adverse events regardless of relatedness to study treatment (>10%) were: infections (URTI: 53%, LRTI: 23%, VZV reactivation: 23%, UTI: 13%), diarrhoea (37%), fatigue (27%), muscle cramps (23%), insomnia (23%), mouth ulcers (13%), peripheral oedema (13%). There was 1 second primary malignancy (SPM) - tAML. This occurred 461 days after commencing RAP. AEs leading to discontinuation were thrombocytopenia (3 patients), central retinal vein thrombosis and tAML. 11 patients tolerated lenalidomide dosing as per protocol, 6 were not increased from 10 to 15mg, 8 required dose modification for AEs (6 to 10mg; 2 to 5mg) and 5 were discontinued due to AEs. Conclusion RAP maintenance improved depth of response post-ASCT with some achieving best response > 8 months after initiation. ORR was 100%, with high rates of CR (20%) and sCR (43%). Correlation between MFC and serological testing appears poor. Many patients who relapsed had poor-risk cytogenetics (+1q), suggesting that these patients may benefit less from RAP maintenance. Disclosures: Off Label Use: Lenalidomide not approved for maintenance therapy post ASCT in Australia. Spencer:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Leopard: A Phase II Study of Maintenance Lenalidomide and Prednisolone Post Autologous Stem Cell Transplantation (ASCT) for Myeloma, Incorporating Minimal Residual Disease Assessments

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2103-2103
Author(s):  
Anna Kalff ◽  
Nola Kennedy ◽  
Patricia A. Walker ◽  
Tiffany T. Khong ◽  
Anthony Schwarer ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Phase Ii ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Response ◽  
Multi Centre Study ◽  
Poor Risk ◽  
Depth Of Response ◽  
Grade 3 ◽  
Minimal Residual

Abstract Background Despite improved outcomes achieved with high dose melphalan conditioned ASCT for Myeloma (MM) patients, relapse is inevitable. Maintenance therapy following ASCT improves the depth of response achieved by induction therapy and prolongs both progression free (PFS) and overall survival (OS). Achievement of stringent (s) complete response (CR) is predictive of improved outcome, as is minimal residual disease (MRD) negativity (-neg) assessed by sensitive techniques such as multiparameter flow cytometry (MFC) of bone marrow (BM). Aim To document disease response changes, PFS/OS in MM patients receiving maintenance lenalidomide and alternate-day prednisolone (RAP) after ASCT. To sequentially quantify MRD in patients achieving a complete response (CR) utilising freeLite chain (FLC) and MFC. To assess safety and tolerability. Methods Phase II, open label, single arm, multi-centre study. Newly diagnosed patients with MM commenced RAP maintenance (lenalidomide 10mg/continuous daily increasing to 15mg after 8/52 and alternate day prednisolone 50mg) 6-8 weeks after a single MEL200 ASCT as part of first-line therapy. RAP continued until toxicity or relapse/progression. Serum for FLC was collected every 2/12, patients achieving CR had serial BM MFC. Statistical analysis: Prism v5.0a. Results 60 patients (M=37, F=23), with a median age of 61 years (range 41-71) commenced RAP maintenance. ISS stage at diagnosis: I: 20, II/III: 37 (3 unknown). 51/60 patients had diagnostic cytogenetics ± FISH performed – 15 had poor risk features (t(4;14), t(14;16), del17p, del13, +1q21), 11/15 had +1q21. After a median 23 months (range 12-36) following initiation of RAP, 33 patients remain on therapy. One patient has been lost to follow-up. Discontinuation was due to relapse/progressive disease (10), AEs (13), physician choice (2), poor compliance (1) and death (1). 15 patients have relapsed/progressed, 11 patients have died; 7 due to MM, 2 due to therapy related AML (tAML) and 2 other. Both the median PFS and OS have not been reached. When looking at the association between survival and poor risk cytogenetics ± FISH, those with +1q21 had both inferior PFS and OS: median PFS was 646 days vs not reached (NR) for those without +1q21 (P=0.04), median OS was 701 days vs NR for those without +1q21(P=0.013). 34 patients improved their post ASCT response on RAP. Best response was CR in 36 (60% - 25 sCR), 21 VGPR (35%) and 2 PR (3%), achieved in a median of 77 days (range, 0-447). 30 of 36 patients in CR went on to have sequential MRD studies: 21/30 were multiply MRD-neg and 9/30 were multiply MRD-pos. There was no difference in PFS between MRD-pos and MRD-neg patients (p=0.3). Of the MRD-neg patients, 16/21 had predominantly normal FLC ratios (sCR), 4/21 MRD-neg patients relapsed, 3 had normal FLC ratios. Of the MRD-pos patients, 6/9 had normal FLC ratios (sCR), 3/9 MRD-pos relapsed. Correlation between MRD neg and sCR was poor (r2=0.05) and there was no difference in relapse rate between patients achieving MRD-neg versus those who achieved sCR. All grade haematologic AEs comprised thrombocytopenia 15/60 (25%)(grade 3/4: 6 [10%]), neutropenia 10/60 (grade 3: 5), and anaemia 5/60 (%)(grade 3: 1). All grade non-haematologic AEs regardless of relatedness to study treatment (>10%) were: infections (URTI: 35%, LRTI: 25%, VZV reactivation: 13%), diarrhoea (38%), insomnia (32%), fatigue (26%), peripheral neuropathy (20%), cramps (18%), hyperglycemia (12%). There have been six second primary malignancies (SPMs) – 2 tAML (onset post C1D1: 15m, 21m), 1 adenocarcinoma of bowel (onset post C1D1: 30m) and 3 skin cancers (SCCs). AEs leading to discontinuation were myelosuppression (9), SPM (2), retinal vein thrombosis (1) and fatigue (1). 24 patients (40%) tolerated lenalidomide dosing as per protocol, 13 were not increased from 10mg/d to 15mg day, and 23 required dose modifications for AEs. Conclusion RAP maintenance improved depth of response post-ASCT (including conversion to deeper response categories > 14months), with high rates of CR/sCR (60%). Neither MFC or FLC demonstrated superiority over the other for prediction of outcome and correlation between the two was poor. Recapitulating earlier findings of an interim analysis, patients with +1q21 had inferior PFS/OS, suggesting that this group may benefit less from RAP maintenance. Only 21% of patients discontinued RAP due to toxicity, comparable to IFM 2005-02 and CALGB 100104 studies. Disclosures Off Label Use: Lenalidomide used as maintenance post-ASCT. Spencer:Takeda: Consultancy, Honoraria; janssen-Cilag: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Honoraria, Research Funding; celgene: Consultancy, Honoraria, Research Funding.

Combined Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) Is Active for Relapsed and Refractory Patients with CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 340-340 ◽  
Author(s):  
William Wierda ◽  
Stefan Faderl ◽  
Susan O’Brien ◽  
Jorge Cortes ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Phase Ii ◽  
Residual Disease ◽  
Response Rates ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3 ◽  
Minimal Residual

New combination regimens for patients with chronic lymphocytic leukemia (CLL) aim to improve complete remission (CR) rates and eliminate minimal residual disease detectible by flow cytomoetry or molecular (PCR) techniques in order to prolong progression-free and overall survival. The complete and overall (OR) response rates to single-agent fludarabine (F) in large phase II studies of previously treated patients with CLL are 12% and 50%, respectively. These rates are improved to 25% CR and 73% OR with chemoimmunotherapy combining F with cyclophosphamide (C) and rituximab (R) (FCR). With FCR, approximately a third of patients achieving CR are rendered negative in bone marrow for the clonal Ig gene by PCR (molecular remission). Alemtuzumab (A) has activity in treating F-refractory patients and in eliminating minimal residual disease. In this phase II study we combined A with FCR (CFAR) to improve response rates and survival in previously treated patients. The CFAR regimen consists of C-250mg/m2 d3-5; F-25mg/m2 d3-5; A-30mg d1,3,5; and rituximab 375–500mg/m2 d2, each 28 days for 6 intended cycles. Methylprednisolone (125mg) on d1 and hydrocortisone (50mg) d2,3,5 are given each course for mAb premedication. Allopurinol 300mg daily is given for tumor lysis syndrome prophylaxis. Antibiotic prophylaxis is TMP-SMX DS twice daily 2–3days/week and valacyclovir 500mg daily, both through all 6 cycles and for 2 months after completion of treatment. CMV antigen in blood is done before each course for monitoring. To date, 31 patients have been enrolled, 21 are evaluable for response, 2 patients are inevaluable, and there was 1 early death. Evaluable patients (17 males) have the following characteristics [median (range)]: age 58yr (46–72), WBC 41K/μl (2–220), HGB 11gm/dl (7.7–14.1), PLT 90K/μl (14–349), β2M 4mg/l (2.5–11.3), and # prior treatments 4 (1–8). Thirteen (62%) and 10 (48%) were refractory to alkylator and F therapy, respectively. Nineteen (90%) and 6 (29%) previously received R and A, respectively. Eleven (52%) previously received FCR and 2 (9%) previously underwent allo-/auto-SCT. At enrollment, 8 (38%) had unfavorable cytogenetics (17p-, 11q-, or complex) by metaphase karyotype. The CR, PR, and OR rates by NCI-WG criteria for these 21 patients were 14%, 38%, and 52% respectively. Five of 8 PRs were categorized as such due to prolonged cytopenia and had no morphologic or flow cytometry evidence of disease. All patients achieving CR were negative for residual disease in bone marrow by 2-color flow cytometry. The median number (range) of CFAR cycles administered were 3 (1–6). Twelve of 21 are currently alive with a median follow-up time of 21 mo. The most common non-hematologic toxicities were grade 1–2 and in order of frequency included fatigue, fever, rash/hives, nausea, URI symptoms, and sinusitis. Grade 3–4 toxicities were much less common and consisted of nausea/vomiting, fever/chills, fatigue, mucositis, consitipation, arthralgia, pneumonia, and shortness of breath. Grade 3 and 4 neutropenia occurred in 23% and 39% of 70 evaulable courses, respectively. Grade 3 and 4 thrombocytopenia occurred in 23% and 16% of 70 evaluable courses, respectively. CMV reactivation was noted in 5/21 of evaluable patients, all cases responded to therapy. This study is ongoing. Early analysis of relapsed or refractory patients with CLL treated with CFAR indicates that this is an active regimen that is well tolerated with expected toxicities.

scholarly journals Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

2016 ◽  
Vol 34 (36) ◽  
pp. 4381-4389 ◽  
Author(s):  
Arend von Stackelberg ◽  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Rupert Handgretinger ◽  
Tanya M. Trippett ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Recommended Dosage ◽  
Disease Response ◽  
Grade 3 ◽  
Minimal Residual

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

Depth of response and minimal residual disease status in ultra high-risk multiple myeloma and plasma cell leukemia treated with daratumumab, bortezomib, lenalidomide, cyclophosphamide and dexamethasone (Dara-CVRd): Results of the UK optimum/MUKnine trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Martin F. Kaiser ◽  
Andrew Hall ◽  
Katrina Walker ◽  
Ruth De Tute ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
Cell Leukemia ◽  
Ultra High Risk ◽  
Grade 3 ◽  
Minimal Residual

8001 Background: Patients with ultra high-risk (UHiR) newly diagnosed multiple myeloma (NDMM) and patients with plasma cell leukemia (PCL) continue to have dismal outcomes and are underrepresented in clinical trials. Recently, improved responses with anti-CD38 monoclonal antibody combination therapy have been reported for NDMM patients. We report here outcomes for NDMM UHiR and PCL patients treated in the OPTIMUM/MUKnine (NCT03188172) trial with daratumumab, cyclophosphamide, bortezomib, lenalidomide, dexamethasone (Dara-CVRd) induction, augmented high-dose melphalan (HDMEL) and ASCT. With final analysis follow-up surpassed in Feb 2021, we report here early protocol defined endpoints from induction to day 100 post ASCT. Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM by central trial genetic (≥2 high risk lesions: t(4;14), t(14;16), t(14;20), gain(1q), del(1p), del(17p)) or gene expression SKY92 (SkylineDx) profiling, or with PCL (circulating plasmablasts > 20%) were included in OPTIMUM across 39 UK hospitals. Patients received up to 6 cycles of Dara-CVRd induction, HDMEL and ASCT augmented with bortezomib, followed by Dara-VR(d) consolidation for 18 cycles and Dara-R maintenance. Primary trial endpoints are minimal residual disease (MRD) status post ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. Data is complete but subject to further data cleaning prior to conference. Results: Median follow-up for the 107 patients in the safety population was 22.2 months (95% CI: 20.6 – 23.9). Two patients died during induction due to infection. Bone marrow aspirates suitable for MRD assessment by flow cytometry (10-5 sensitivity) were available for 81% of patients at end of induction and 78% at D100 post ASCT. Responses in the intention to treat population at end of induction were 94% ORR with 22% CR, 58% VGPR, 15% PR, 1% PD, 5% timepoint not reached (TNR; withdrew, became ineligible or died) and at D100 post ASCT 83% ORR with 47% CR, 32% VGPR, 5% PR, 7% PD, 10% TNR. MRD status was 41% MRDneg, 40% MRDpos and 19% not evaluable post induction and 64% MRDneg, 14% MRDpos and 22% not evaluable at D100 post ASCT. Responses at D100 post ASCT were lower in PCL with 22% CR, 22% VGPR, 22% PR, 22% PD, 12% TNR. Most frequent grade 3/4 AEs during induction were neutropenia (21%), thrombocytopenia (12%) and infection (12%). Grade 3 neuropathy rate was 3.7%. Conclusions: This is to our knowledge the first report on a trial for UHiR NDMM and PCL investigating Dara-CVRd induction and augmented ASCT. Response rates were high in this difficult-to-treat patient population, with toxicity comparable to other induction regimens. However, some early progressions highlight the need for innovative approaches to UHiR NDMM. Clinical trial information: NCT03188172.

scholarly journals PF630 MINIMAL RESIDUAL DISEASE MONITORING AND DEPTH OF RESPONSE IN MULTIPLE MYELOMA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 268
Author(s):  
J. Martinez-Lopez ◽  
S. Wong ◽  
N. Shah ◽  
N. Bahri ◽  
T. Martin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disease Monitoring ◽  
Depth Of Response ◽  
Minimal Residual Disease Monitoring ◽  
Minimal Residual

Minimal residual disease in multiple myeloma: an important tool in clinical trials

2021 ◽  
Vol 16 ◽  
Author(s):  
Alessandro Gozzetti ◽  
Monica Bocchia
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
New Drugs ◽  
Next Generation ◽  
Depth Of Response ◽  
Next Generation Sequencing Ngs ◽  
Future Therapy ◽  
Minimal Residual

: Minimal residual disease (MRD) detection represents a great advancement in multiple myeloma. New drugs are now available that increase depth of response. The International Myeloma Working Group recommends the use of next-generation flow cytometry (NGF) or next-generation sequencing (NGS) to search for MRD in clinical trials. Best sensitivity thresholds have to be confirmed, as well as timing to detect it. MRD has proven as the best prognosticator in many trials and promises to enter also in clinical practice to guide future therapy.

Moving Beyond Autologous Transplantation in Multiple Myeloma: Consolidation, Maintenance, Allogeneic Transplant, and Immune Therapy

2016 ◽  
pp. 210-221 ◽  
Author(s):  
Amrita Krishnan ◽  
Ravi Vij ◽  
Jesse Keller ◽  
Binod Dhakal ◽  
Parameswaran Hari
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
The Other ◽  
Novel Agents ◽  
Patient Specific ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Minimal Residual

For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses. Though the consolidation strategy remains largely confined to clinical trials, significant data support the efficacy of consolidation in improving the depth of response and outcomes. There are also increasing rates of minimal residual disease–negativity with additional consolidation therapy. On the other hand, maintenance with novel agents post-transplant is well established and has been shown to improve both progression-free and overall survival. Evolving paradigms in maintenance include the use of newer proteasome inhibitors, immunotherapy maintenance, and patient-specific maintenance—a concept that utilizes minimal residual disease as the primary driver of decisions regarding starting or continuing maintenance therapy. The other approach to overcome residual disease is immune therapeutic strategies. The demonstration of myeloma-specific alloimmunity from allogeneic transplantation is well established. More sophisticated and promising immune approaches include adoptive cellular therapies, tumor vaccines, and immune checkpoint manipulations. In the future, personalized minimal residual disease–driven treatment strategies following ASCT will help overcome the residual disease, restore multiple myeloma–specific immunity, and achieve sustained disease control while minimizing the risk of overtreatment.

High Efficacy and Good Tolerability with Rituximab In Vivo Purging Followed by High Dose Chemotheraphy and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) in Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4626-4626
Author(s):  
Yuankai Shi ◽  
Sheng Yang ◽  
Xiaohong Han ◽  
Peng Liu ◽  
Xiaohui He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Median Time ◽  
Residual Disease ◽  
High Dose ◽  
Platelet Recovery ◽  
Minimal Residual

Abstract Purpose: High-dose chemotherapy (HDC) supported by APBSCT has been shown to be superior to standard therapy in NHL. However, many patients relapse due to minimal residual disease (MRD) in vivo or in the graft. Rituximab has the potential to clear both blood and bone marrow of malignant CD20+ cells, prompting this multicenter trial of in vivo purging with rituximab and HDC with APBSCT in China. Methods: Cyclophosphamide 4g/m2 was used as the mobilization regimen, CY/TBI, BEAM or CBV could be used as HDC at the discretion of the institution. Four infusions of rituximab (375 mg/m2) were given: one day before mobilization, one day before harvesting, one day before transplantation and on day 8 after transplantation. BCL-2/Ig-H translocation was measured as a marker of minimal residual disease in blood or bone marrow before mobilization and during transplantation using real-time quantitative PCR. Results: Thirty-one patients from 12 centers with histologically proven CD20+ NHL (28 aggressive, 3 indolent NHL) were enrolled. Twenty-four patients were previously untreated, and 7 patients had relapsed disease. Median yields of CD34+ cells and mononuclear cells were 5.9×106/kg and 4.4×108 /kg respectively. Median time to recovery of WBC >1.5×109/L, ANC >0.5×109/L and platelets >20×109/L after APBSCT was 10 days in each case. Median time to platelet recovery >50×109/L was 13 days. Generally, this therapeutic strategy was well tolerated with few side effects attribute to rituximab. All patients achieved a complete remission after APBSCT. At a median-follow-up of 12 months, overall survival and progression-free survival (PFS) are 87% and 73% respectively for all patients. In patients with aggressive NHL, overall survival and PFS are 85% and 73% respectively and in indolent NHL are 100% and 67% respectively. PFS and overall survival were slightly higher in previously untreated compared with relapsed patients (88% vs. 83% for PFS, 73% vs. 69% for overall survival). One of five 5 patients who were initially found to be PCR-positive and achieved PCR-negative status subsequently experienced progression accompanied by a return to PCR positivity. The remaining four patients are still in complete remission and are PCR negative. Conclusion: These results suggest that the regimen of rituximab combined with HDCT and APBSCT is effective and well tolerated for the treatment of patients with NHL.

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