scholarly journals Percutaneous Cryoablation of Renal Tumors: Initial Indian Experience

2022 ◽  
Author(s):  
Ujjwal Gorsi ◽  
Rishabh Jain ◽  
Akash Bansal ◽  
Naveen Kalra ◽  
Mandeep Kang ◽  
...  
Keyword(s):  
Residual Disease ◽  
Early Stage ◽  
Clinical Success ◽  
Complete Response ◽  
Late Recurrence ◽  
Tertiary Hospital ◽  
Renal Tumors ◽  
Short Term ◽  
Nephrometry Score

Abstract Objective The purpose of this study was to report short-term outcomes of cryoablation of early-stage renal tumors (T1a and T1b) at a tertiary hospital in India. Methods This was a retrospective study of consecutive patients who underwent cryoablation for renal cell carcinoma (RCC) from November 2018 to June 2020. Cryoablation was performed under combined ultrasound and computed tomography guidance using a helium-argon cryoablation system. Tumor number, size, location, nephrometry score, relationship of the tumor with pelvicalyceal system, and adjacent organs were tabulated, and technical and clinical success evaluated. Early and late recurrence and complications were also assessed. Results Eleven patients (median age: 62 years) with 11 tumors underwent cryoablation. The mean tumor size was 2.58 cm (range: 1.62–5.62 cm) with 10 lesions being T1a and one lesion T1b. Tissue sampling was done in 9/11 patients, 3 were papillary RCC and the rest, clear cell RCC. In two patients, the tumor was completely endophytic, three patients had partially endophytic tumors while 6 patients had exophytic lesions. The median nephrometry score was 6 (range: 4–11, Mode 4). Technical success was achieved in all patients. Complete response was achieved in 81% (9/11) of the patients at 1-month follow-up. Median follow-up period was 6 months. Two patients showed residual disease on follow-up imaging at 1 and 3 months, respectively. Conclusion Cryoablation is a promising, relatively new minimally invasive therapy for treating small renal tumors in India. It is safe, technically feasible, and shows excellent short-term efficacy.

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Second Primary ◽  
Cell Transplant ◽  
Open Label ◽  
Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

scholarly journals ACUTE LYMPHOBLASTIC LEUKEMIA EXPERIENCE: EPIDEMIOLOGY AND OUTCOME OF TWO DIFFERENT REGIMENS

2013 ◽  
Vol 5 (1) ◽  
pp. e2013024 ◽  
Author(s):  
Salah Abbasi ◽  
Faten Maleha ◽  
Muhannad Shobaki
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Medical Records ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Complete Response ◽  
Cancer Center ◽  
Poor Prognostic Factor ◽  
Minimal Residual Disease Monitoring ◽  
Adult Acute Lymphoblastic Leukemia

Objectives. Accurate data about adult acute lymphoblastic leukemia (ALL) are lacking. We aim to assess demographics, prognostic factors, and outcome of ALL therapy at King Hussein Cancer Center (KHCC) in Jordan, and to compare the efficacy of two protocols.Methods. We reviewed medical records of adults diagnosed and treated for ALL at KHCC from January, 2006 to December, 2010.Results. Over a 5-year period, 108 patients with ALL were treated (66 with the Hyper-CVAD regimen, and 42 with the CALGB 8811 regimen). Median age at diagnosis was 33 years, with 63% males. The most common immunophenotype was CD10-positive common ALL, and 16% have BCR-ABL translocation. Complete response (CR) rate was 88%. After a median follow-up of 32 months (range, 10-72 months), the median survival (MS) was 30 months, and CR duration (CRD) was 28 months. In the multivariate analysis, the presence of BCR-ABL translocation was the only poor prognostic factor with lower MS of 23 months (p<0.01). There was no difference in MS or CRD between the two used regimens.Conclusion. International protocols for adult ALL were successfully applied to our patients. There is no difference in efficacy between Hyper-CVAD and CALGB 8811 regimens. Future protocols for adult ALL should incorporate new targeted agents and minimal residual disease monitoring to improve outcome.

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Christian W. Scholz ◽  
Antonello Pinto ◽  
Werner Linkesch ◽  
Ola Lindén ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Residual Disease ◽  
Standard Procedure ◽  
Complete Response ◽  
Molecular Response ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Multicenter Phase

Purpose We report on a multicenter phase II trial of 90yttrium-ibritumomab-tiuxetan (90YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods Fifty-nine patients with CD20+ FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received 90YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of 90YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. Results Six months after treatment with 90YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after 90YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). Conclusion 90YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after 90YIT appear to have long- lasting responses.

Practice patterns in post-treatment surveillance in patients with primary epithelial ovarian cancer

2020 ◽  
pp. ijgc-2020-001522
Author(s):  
Joseph DeMari ◽  
Monica Hagan Vetter ◽  
Shruthi Chandra ◽  
John L Hays ◽  
Ritu Salani
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Practice Patterns ◽  
Early Stage ◽  
Gynecologic Oncology ◽  
Complete Response ◽  
Response To Therapy ◽  
Primary Therapy ◽  
Advanced Stage

BackgroundThe Society of Gynecologic Oncology created guidelines to standardize cost-effective clinical surveillance for detection of recurrence of gynecologic cancers.ObjectiveTo determine practice patterns for surveillance of primary ovarian cancer after complete response to therapy and to identify the percentage of clinicians who follow the surveillance guidelines endorsed by the Society of Gynecologic Oncology.MethodsA single-institution retrospective cohort study was conducted including patients with epithelial ovarian cancer with a complete response to primary therapy between January 2012 and December 2016. Patients were excluded if they were participating in clinical trials that required routine imaging. Data on surveillance and recurrence were collected. Descriptive statistics as well as Fisher’s exact test and chi-square test were performed due to the exploratory nature of the study.ResultsA total of 184 patients met the inclusion criteria. Median follow-up for the cohort was 37 months (range 6–80). Surveillance was completed in compliance with Society of Gynecologic Oncology guidelines in 78% of patients. Of 39 visits that were non-compliant, 44% (17) were patient initiated (scheduling conflict, missed appointment), 15% (6) were due to the provider intentionally scheduling alternative follow-up, while 41% (16) were off schedule due to problem visits (patient complaint of symptoms). Patients with early-stage cancers were more likely than advanced-stage patients to be non-compliant (33% vs 15%, p=0.006). Patients with non-serous histologies had a higher frequency of non-compliance (31% vs 16%, p=0.035). When stratified by early versus advanced stage, there was no difference in progression-free survival or overall survival based on compliance.ConclusionsOverall, there was a relatively high rate of compliance with Society of Gynecologic Oncology surveillance guidelines for patients with epithelial ovarian cancer. Patients with non-serous histologies and patients with early-stage disease had a higher rate of non-compliance, and these patients may represent special groups that would benefit from additional survivorship education.

Rechallenge with trabectedin in patients with responding myxoid liposarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10575-10575 ◽  
Author(s):  
R. Sanfilippo ◽  
F. Grosso ◽  
E. Virdis ◽  
C. Morosi ◽  
J. C. Tercero ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Residual Disease ◽  
Myxoid Liposarcoma ◽  
Complete Response ◽  
Response To Therapy ◽  
Patient Response ◽  
Complete Surgical Resection ◽  
Definition Of ◽  
Access Program

10575 Background: To determine the efficacy of rechallenge with trabectedin (T) in patients with myxoid liposarcoma who were responding to T at the time of discontinuation but subsequently developed progressive disease. Methods: Since September 2002, 32 patients with recurrent or advanced myxoid liposarcoma received T at our institution within an expanded access program. We report herein 8 patients who received T for a median of 10 cycles (range 5–15) prior to discontinuation. We used RECIST criteria to classify patient response to therapy. During the initial administration of T, a CR had been observed in 2 patients, a PR in 3 patients, SD in 2 patients, and one had had tumor shrinkage but did not meet RECIST definition of PR. The median PFS was 24 months from treatment start, and 14 months (range 9–27) from treatment-end. In 6 of the 8 patients, the treatment had been discontinued in the absence of any evidence of disease: 4 patients had undergone complete surgical resection (R0) of residual disease and 2 patients had achieved a radiological complete response (CR). The other two patients stopped treatment voluntarily, one with a partial response (PR) and one with stable disease (SD). All these patients resumed treatment at the time of progression. Results: Following rechallenge with T, no PD was seen at first assessment, and no patients had to discontinue or reduce the dose due to toxicity. Response rate according to RECIST was 50%. At a median follow up of 7 months (range 2.7–12), the median TTP has not yet been reached. Treatment is still ongoing in 5 patients. Conclusions: Rechallenge with T can be beneficial in some patients with myxoid liposarcoma. If further data confirm this, treatment of progressing patients previously responding to T may include this option. Furthermore, studies on optimization of treatment duration upfront may be worthwhile. [Table: see text]

Inotuzumab ozogamicin (IO) combined with mini-hyper-CVD as salvage therapy for patients (pts) with R/R acute lymphoblastic leukemia (ALL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7025-7025 ◽  
Author(s):  
Rita Assi ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Susan Mary O'Brien ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Intrathecal Chemotherapy ◽  
Free Survival ◽  
Low Intensity ◽  
Transplant Candidates ◽  
Grade 3

7025 Background: Outcome of pts with R/R ALL is poor. IO, a CD22 monoclonal antibody bound to a toxin, calicheamicin, has single-agent activity in R/R ALL with response rate of 80% and median survival of 7.7 months. Adding IO to low-intensity chemotherapy might further improve clinical outcomes. Methods: Pts ≥18 years with R/R ALL were eligible. Chemotherapy was of lower intensity than standard hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction (DR), no anthracycline, methotrexate at 75% DR, cytarabine at 0.5 g/m2 x 4 doses). Rituximab (if CD20+ blasts) and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses at a dose of 1.8 mg/m2 for cycle 1 then 1.3 mg/m2 for subsequent cycles. After the occurrence of veno-occlusive disease (VOD), IO was modified to 1.3 mg/m2 for cycle 1 followed by 1.0 mg/m2 for subsequent cycles. Results: Sixty pts with a median age of 35 years (range 18-87) were treated. Overall, 47 pts (80%) responded, 32 of them (54%) achieving complete response. The overall minimal residual disease negativity rate among responders was 82%. Grade 3-4 toxicities included prolonged thrombocytopenia (79%), infections during induction and consolidations (52%, and 73% respectively), and hyperbilirubinemia (13%). VOD of any grade occurred in 9 patients (15%). At a median follow-up of 19 months, the median relapse-free survival (RFS) and overall survival (OS) were 9 and 11 months, respectively. The 2-year RFS and OS rates were 33% and 38%. The 2-year OS rates for patients treated in salvage (S)1, S2, and S3 and beyond were 53%, 0%, and 34%, respectively (p = 0.005). When compared to IO monotherapy in a similar pts population, a significant improvement in OS was observed (11 and 6 months, respectively; p = 0.003). Conclusions: The combination of IO with low-intensity mini-hyper-CVD chemotherapy is effective in pts with R/R ALL. Results are encouraging and appear superior to those obtained with IO alone, particularly in pts treated in S1. The risk of VOD should be considered carefully for transplant candidates and pts with previous liver damage. Lower dose of weekly schedules of IO are being explored Clinical trial information: NCT01371630.

Vinblastine, Mitoxantrone and Prednisone (MVP) Followed by Involved Field Radiotherapy (IF-XRT) for Early Clinical Stage Hodgkins’s Lymphoma: Long Term Follow-Up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2677-2677
Author(s):  
Danielle Shafer ◽  
Hossein Borghaei ◽  
Michael Millenson ◽  
Nicos Nicolaou ◽  
Tahseen I. Al-Saleem ◽  
...  
Keyword(s):  
Overall Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Complete Response ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Combined Modality Treatment ◽  
Grade 3

Abstract Background: The treatment of early stage Hodgkin’s lymphoma (HL) continues to evolve in attempt to improve the safety profile of the regimens and decrease their long-term toxicities. Treatment related mortality exceeds that from HL after 12 to 15 years. In light of the potential long-term complications associated with irradiation and chemotherapy, particularly pulmonary and cardiac toxicity, alternative approaches minimizing exposure to drugs with long-term organ toxicity have been examined. Objectives: We evaluated a novel regimen of MVP and IF-XRT for non-bulky early-stage HL. The primary outcomes were response rate and freedom from disease progression. Secondary outcomes were toxicity, specifically pulmonary and cardiac dysfunction. Methods: Patients were enrolled in this multi-site phase 2 study between 1995 and 1999. Eligible patients were 18 years of age or older, had ECOG performance status 0–2 and pathologically confirmed, clinically staged non-bulky Stage I or II HL. Patients received a minimum of four cycles of mitoxantrone 8mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 15 of each 28-day cycle. Prednisone 100mg was given orally days 1 to 5 and 15 to 19. Chemotherapy was continued for two additional cycles after complete response, up to eight cycles. Patients then received IF-XRT (30.6 Gy-39.6 Gy) four weeks after completion of chemotherapy. G-CSF was not used as primary prophylaxis. Results: Thirty-four patients were evaluated for response in a final review. A total of 32 patients (94%) achieved a complete remission after combined therapy. Thirty patients (88%) achieved a complete response after chemotherapy alone. At a median follow-up of 49 months (range 16.9–79.7 months), 10 patients had relapsed, and three deaths were documented. None of the deaths occurred during treatment. The median time to progression was 30 months. The overall survival and disease-free survival rates at 5 years were 90% (95% confidence interval [CI], 73–97%) and 78% (95% CI, 58–89%), respectively. The treatment was well tolerated without significant grade 3/4 toxicity. (Grade 3/4 leukopenia 18% of patients; neutropenia 28%) There were no significant changes in DLCO or left ventricular ejection fraction at 12 months observed after chemotherapy. Twenty-one patients received only 4 cycles of chemotherapy; the median dose intensity for the entire group was 85%. Conclusions: As the management of early-stage HL continues to evolve in attempt to reduce long-term toxicity, this trial serves as a reminder of the balance required between efficacy and toxicity in this largely curable population. In this relatively well-tolerated regimen, there was minimal long-term toxicity, but a high number of relapses, most of which were successfully salvaged with resultant excellent 5-year overall survival rates. As the treatment for early-stage HL moves forward, there will undoubtedly be further attempts to modify the ABVD backbone. We await those results as well as long term data from the German Hodgkin Study group investigating reduction of combined modality treatment (HD10) in a similar patient population.

Consolidation Therapy with Subcutaneous (SC) Alemtuzumab After Fludarabine and Rituximab (FR) Induction Therapy Improves the Complete Response (CR) Rate in Chronic Lymphocytic Leukemia (CLL) and Eradicates Minimal Residual Disease (MRD) but Is Associated with Severe Infectious Toxicity: Final Analysis of CALGB Study 10101.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 210-210
Author(s):  
Thomas S Lin ◽  
Kathleen A Donohue ◽  
John C. Byrd ◽  
Margaret S Lucas ◽  
Eva Hoke ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Consolidation Therapy ◽  
Varicella Zoster ◽  
Grade 3

Abstract Abstract 210 Background: Alemtuzumab (Campath-1H) is approved for the treatment of CLL. CALGB sought to determine whether alemtuzumab can improve the CR rate and eradicate MRD after induction chemoimmunotherapy by performing a phase II study administering FR followed by alemtuzumab consolidation to previously untreated, symptomatic CLL patients (pts). We previously reported preliminary toxicity data (Lin et al. ASH 2007) and now report final toxicity and response data. Methods: Pts received fludarabine 25 mg/m2 IV on days 1–5, and rituximab 50 mg/m2 IV on day 1, 325 mg/m2 on day 3, and 375 mg/m2 on day 5 of cycle 1 and then only on day 1 of cycles 2–6, repeated every 28 days for up to 6 cycles. Four months after the last fludarabine dose, pts with stable (SD) or responsive disease by NCI 96 criteria received SC alemtuzumab 3 mg on day 1, 10 mg on day 3, and 30 mg on day 5, and then thrice weekly thereafter for 6 weeks (18 total doses). Pts received standard Pneumocystis (PCP) and Varicella zoster virus prophylaxis and were monitored weekly by PCR for Cytomegalovirus (CMV) viremia. When unacceptable serious infectious toxicity was noted in pts who received alemtuzumab after achieving CR from FR induction, the study was amended so that only PR or SD pts received alemtuzumab after FR. Results: Median age of pts (n=102) was 61 years (range, 23–82), 74% were male, and 30% were Rai stage III/IV. FR was well tolerated; 93% of pts received at least 3 cycles, and 77% completed all 6 cycles. Overall, complete and partial response (OR, CR, PR) rates after FR induction were 90%, 29% and 61%, and 15% were MRD negative by flow cytometry. Fifty-eight pts received alemtuzumab, and 42 (72%) completed the planned 6 weeks of therapy. OR, CR, and PR rates after alemtuzumab (n=58) were 91%, 66% and 26%, and 50% were MRD negative. Twenty-eight of 45 pts (62%) in PR after FR who received alemtuzumab attained CR. Of 11 pts in CR after FR who received alemtuzumab, 5 were MRD negative prior to consolidation and 3 of the other 6 converted to MRD negative afterwards. By intent-to-treat for all patients enrolled, OR, CR, and MRD negativity were attained by 90%, 57% and 42% of pts. With a median follow up of 34 months, median progression free survival (PFS) was 37 months (95% CI, 33–43 months); PFS was 73% and overall survival (OS) 86% at 2 years. Two-year PFS (76% vs 70%, p=0.54) and OS (84% vs 88%, p=0.89) were similar for pts who did and did not receive alemtuzumab. Similarly, there were no differences in PFS or OS among the 30 pts in CR after FR whether or not they received alemtuzumab, although the numbers were small. Grade 3–4 neutropenia and thrombocytopenia were observed in 43% and 19% of pts during alemtuzumab therapy. Grade 3–4 non-hematologic toxicity was observed in 41% of pts, including 19% infections and 19% febrile neutropenia, during alemtuzumab therapy. As we previously reported, 5 pts in CR after FR who received alemtuzumab died from infections (viral meningitis, Listeria meningitis, Legionella pneumonia, CMV and PCP pneumonia), and one pt in PR after FR who received alemtuzumab died of Epstein-Barr (EBV) viremia without evidence of EBV lymphoma. These grade 5 toxicities occurred both during and for up to 7 months after alemtuzumab therapy. Conclusions: Alemtuzumab consolidation improved the CR and MRD negative rates after FR induction. However, alemtuzumab consolidation resulted in significant toxicity, particularly severe infections in pts who achieved a CR after FR induction. Longer follow up is needed to determine if the improved CR and MRD negative rates following alemtuzumab consolidation will eventually result in improved PFS or OS, especially among pts who achieved a PR after FR induction. Disclosures: Lin: GlaxoSmithkline: Consultancy, Employment; Genentech: Consultancy; Bayer: Consultancy. Off Label Use: Use of alemtuzumab as consolidation therapy. Byrd:Genentech: Consultancy, Research Funding. Link:Genentech: Consultancy. Rai:Genentech: Consultancy; Bayer: Consultancy.

Sustained High Rates of Complete Response and Minimal Residual Disease Negativity after 8 Cycles of Carfilzomib (CFZ), Lenalidomide (LEN), and Dexamethasone (DEX) Followed By 2 Years of Lenalidomide Maintenance (CRd-R) in Patients with High-Risk Smoldering Multiple Myeloma: Updated Results of Clinical and Correlative Phase 2 Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3339-3339 ◽  
Author(s):  
Dickran Kazandjian ◽  
Neha S Korde ◽  
Mark Roschewski ◽  
Sham Mailankody ◽  
Candis Morrison ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Combination Therapy ◽  
Minimal Residual Disease ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Response ◽  
Risk Of Progression ◽  
Minimal Residual

Abstract Background: High-risk smoldering multiple myeloma (HR-SMM) is a plasma cell dyscrasia which has a 5-year risk of progression to symptomatic multiple myeloma (MM) of approximately 75% based on current risk models. With the availability of novel therapies, early treatment may decrease the risk of progression and prolong survival as evidenced by the recent QuiRedex study results. More recently, studies have demonstrated that triplet regimens are superior to doublet in MM and whole exome sequencing in HR-SMM is indicative of treatment susceptible biology in early disease; supporting the use of effective combination therapy as early intervention. Expanding on our initial results using modern CRd-R therapy in HR-SMM patients (Korde et al. JAMA Onc 2015) we show unprecedented high rates of obtained and sustained complete response (CR) and minimal residual disease negativity (MRDneg CR) in an expanded cohort of patients with a median follow-up of ~3 years. Methods: Treatment-na•ve patients with HR-SMM (IMWG 2010 criteria; Mayo or PETHEMA models) were treated for 8 cycles (28-day cycles) with CFZ 20/36 mg/m2 IV days 1, 2, 8, 9, 15, 16; LEN 25 mg PO days 1-21, and DEX 20/10 mg IV/PO days 1, 2, 8, 9, 15, 16, 22, 23. Transplant eligible patients underwent stem cell collection after ≥4 cycles of CRd and then continued CRd treatment (i.e. by-default-delayed high-dose melphalan with autologous stem cell transplant; HDM-ASCT). After 8 cycles of combination therapy, patients with SD or better received 2 years of LEN 10 mg PO maintenance. The primary objective was best response (ORR), followed by secondary objectives of progression free survival (PFS) and response duration (DoR) which were assessed after every cycle of induction and every 90 days during maintenance. Correlative studies including assessment of minimal residual disease (MRD) by multi-color flow cytometry (bone marrow aspirate; 10-5 sensitivity) as defined by updated 2016 IMWG response criteria were performed after 8 cycles of induction and 1 and 2 years of maintenance LEN. Results: Eighteen patients meeting eligibility criteria were enrolled (data-lock 7/20/2016). Demographics and disease characteristics are shown in Table 1. Best ORR and >= VGPR rate (n=18) with CRd-R was 100% (Table 2). The proportion of patients who obtained stringent CR/CR after 8 cycles of induction, 1 year of maintenance and 2 years of maintenance was 61%, 89%, and 89%, respectively. Of evaluable patients who achieved at least a CR, the proportion of patients who obtained MRD negativity (MRDneg CR) at the same time-points was 91%, 71%, and 75%, respectively. DoR and PFS at 36 months was 94% and overall survival with a median follow-up duration of 31 months was 100%. Toxicities Grade 3-4 occurring in >1 patient included lymphopenia (39%), neutropenia (28%), anemia (22%), diarrhea (17%), lung infection (17%), hypophosphatemia (11%), and thromboembolic event (11%). Significant serious adverse events included CHF which occurred in one patient. Conclusions: Early treatment of HR-SMM with modern CRd-R combination therapy with by-default-delayed HDM-ASCT resulted in unprecedented high rates of CR and MRDneg CR after 8 cycles of CRd. Following 2 years of additional LEN maintenance therapy, the CR and sustained MRDneg CR rates were 89% and 69%, respectively. Given the significant risk of progression to symptomatic MM and associated life limiting end-organ damage, early intervention for patients with HR-SMM with effective triplet-based therapies may be warranted. This first proof-of-principle study has thus far demonstrated exceptional clinical benefit. Therefore, this study will be re-opened to enrollment and long-term follow up results collected to expand on these promising results. Updated results will be presented at the Annual Meeting. Disclosures Korde: Medscape: Honoraria. Bhutani:Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Landgren:BMS: Honoraria; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Takeda: Honoraria.

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