Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9543-9543
Author(s):  
Alison Margaret Weppler ◽  
Laetitia Da Meda ◽  
Ines Silva ◽  
Wen Xu ◽  
Giovanni Grignani ◽  
...  
Keyword(s):  
Median Time ◽  
Checkpoint Inhibitors ◽  
Initial Response ◽  
Leptomeningeal Disease ◽  
Treatment Cessation ◽  
Cns Involvement ◽  
Duration Of Treatment ◽  
Disease Characteristics ◽  
Best Response

9543 Background: mMCC is a rare, aggressive neuroendocrine cancer which often occurs in older patients (pts) with multiple comorbidities. While initial response rates to ICI are high, optimal treatment duration, durability of response after treatment cessation and response to retreatment with ICI is unknown. Methods: mMCC pts from 12 international centres who received at least one dose of ICI and subsequently stopped treatment without progression for a minimum of 12 weeks were studied. Demographics, disease characteristics and treatment course were examined. Results: 40 pts with mMCC were included. Pt characteristics are summarised in Table. Median time on treatment was 13.5 months (range 1 to 35). Median time to best response was 4.5 months (range 1 to 17) and median time receiving treatment after best response was 8 months (range 0 to 29). 25 pts (63%) stopped primarily due to being in a complete or partial response (CR or PR), 9 (23%) due to toxicity and 6 (15%) due to other reasons, primarily pt choice or comorbidities. At time of discontinuation, 30 pts (75%) were in a CR, 8 (20%) in a PR and 2 pts (5%) had stable disease (SD). After a median follow up of 12 months from discontinuation, 14 pts (35%) have progressed (PD); 5 (36%) at a previous site, 5 (36%) at a new site and 4 (29%) at both. PD occurred after a median of 5.5 months (range 4 to 29) off treatment. 4 pts (29%) had a CNS recurrence, none of whom previously had CNS involvement. Pts in CR at time of discontinuation were less likely to progress (CR: 26% PD vs non-CR: 67% PD, p=0.044), but still had a considerable rate of PD (CR: 26%, PR: 57%, SD: 100%). Those who progressed had numerically less cycles of ICI prior to treatment cessation (17 vs 32, p>0.05). Baseline disease factors, time to best response and duration of treatment after best response were not associated with PD. ICI was restarted in 8 of 14 pts (57%) with PD, with response rate to retreatment of 75% (4 CR, 2 PR, 1 SD, 1 PD – pt with leptomeningeal disease). Median time to best response at retreatment was 3 months (range 2 to 7), with all responses ongoing after a median of 10 months back on treatment. 3 pts had an isolated site of PD successfully treated with radiation therapy and remain in remission off ICI. Conclusions: ICI responses in mMCC do not appear as durable off treatment as in other cancers, including in patients who achieve a CR. Ongoing treatment should be considered, though initial data on response to retreatment is promising.[Table: see text]

Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9533-9533
Author(s):  
Ines Pires Da Silva ◽  
Judith M. Versluis ◽  
Tasnia Ahmed ◽  
Douglas Buckner Johnson ◽  
Jennifer Soon ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Initial Response ◽  
Best Supportive Care ◽  
First Line ◽  
Disease Characteristics ◽  
Best Response ◽  
Investigational Drugs ◽  
Ecog Ps

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient

2019 ◽  
Vol 26 (2) ◽  
pp. 496-499 ◽  
Author(s):  
Saadettin Kilickap ◽  
Deniz C Guven ◽  
Oktay H Aktepe ◽  
Burak Y Aktas ◽  
Omer Dizdar
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Complete Response ◽  
Duration Of Treatment ◽  
Treatment Protocols ◽  
Real Life Data ◽  
Heavily Pretreated ◽  
Drug Free

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

Real-world (rw) clinical outcomes for advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) treated with second line (2L) ramucirumab plus docetaxel (R+D) post frontline (1L) platinum based chemotherapy plus immune checkpoint inhibitors (Pt + ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20727-e20727
Author(s):  
Jeffrey Melson Clarke ◽  
Raina Mathur ◽  
Cliff Molife ◽  
Marta Batus ◽  
Victoria Jennifer Stefaniak ◽  
...  
Keyword(s):  
Disease Control ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Community Practice ◽  
Best Response ◽  
First Response ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response & rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged < 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), & 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) & rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) & median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.

Outcome after second stem cell transplantation for relapsed multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8118-8118 ◽  
Author(s):  
L. Simpson ◽  
R. Verma ◽  
S. Kumar ◽  
M. Lacy ◽  
A. Dispenzieri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Standard Of Care ◽  
Best Response ◽  
High Risk Disease ◽  
Viable Approach ◽  
Median Interval

8118 Background: Autologous stem cell transplantation (ASCT) improves survival and remains the standard of care for patients with newly diagnosed myeloma considered eligible for transplant. However, ASCT is not curative and patients relapse after a median interval of 24–30 months. While new therapeutic options have become available for relapsed MM, repeat ASCT remains an option especially when previously collected stem cells are available. The outcome of pts going to a second SCT in the relapsed setting has not been studied extensively. Methods: We identified pts with myeloma who received a second SCT from a prospectively maintained database. Planned tandem ASCTs were excluded. 56 pts received a second SCT for relapsed MM, including 11 allogeneic SCTs. Among the 45 second ASCTs, 5 were followed by reduced intensity allogeneic SCT and were analyzed with the allogeneic group. Results: The median age at second ASCT was 60.2 yrs (range, 41.3–74.4) and 27 (68%) were males. The median time to second ASCT from diagnosis, first ASCT and relapse were 47.4 mos (22.8–158.6), 36.3 mos (13.5–129.8) and 7.2 mos (1–32) respectively. Among patients receiving second APBSC, 14 (35%) patients were alive with a median follow up of 10.5 mos (1–45 mos). All patients received melphalan conditioning. The median time to neutrophil engraftment was 15 days and platelet engraftment was 16 days. The median hospitalization was 4 days (range 0–33) and there was one transplant related death in the group. The best response included 13 pts with CR (33%), 4 with VGPR (10%), and 19 with PR (48%). MM has relapsed in 22 (55%) pts with a median PFS of 12.5 mos from second ASCT. The median estimated OS from diagnosis, first ASCT and second ASCT were 100.5 mos, 65.9 mos, and 30.6 mos respectively. Among the 16 pts receiving allogeneic SCT, 8 pts (50%) were alive at analysis with a median PFS and OS from transplant of 17.9 mos and 33.5 mos respectively. Conclusions: Second ASCT as salvage therapy for relapsed MM is a viable approach and has a favorable outcome in this selected group of patients. The toxicity, engraftment kinetics, hospitalization and the response rates are comparable to patients undergoing initial ASCT. Allogeneic SCT with or with out a preceding ASCT results in comparable survival in selected patients with high risk disease. No significant financial relationships to disclose.

Erlotinib (E) in non small cell lung cancer (NSCLC) patients (pts) ≥75 years old with comorbidities (cM): Experience at a tertiary referral center.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19111-e19111
Author(s):  
Konstantinos N. Syrigos ◽  
Evangelos Sarris ◽  
Alexios S Strimpakos
Keyword(s):  
Side Effects ◽  
Disease Control ◽  
Performance Status ◽  
Egfr Mutations ◽  
Time To Progression ◽  
Duration Of Treatment ◽  
Tertiary Referral Center ◽  
Best Response ◽  
Nsclc Patients

e19111 Background: Besides chemotherapy, E is another option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM, but in clinical practice most suffer from cM. Methods: Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts ≥75 yrs for demographics, clinical data and Tx details. Results: 233/1221 NSCLC pts received E at any line. 53/233 (23%) were ≥75 yrs old. Male:female ratio was 34:19 and median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous cell, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of treatment was 79 days (range 9-662). 35/46 pts experienced side effects (s.e) [rash n=29, diarrhea n=17] which led to treatment discontinuation in 12pts. Pts with abnormal creatinine clearance (n=13) were more likely to stop treatment due to s.e (6/13 versus 6/33). 17/46 pts (37%) achieved disease control (5 PR, 12 SD) and a time to progression (TTP) of 157 days (range 106-662, 95% CI 132.79-270,74) while 22/46 pts had PD as best response (TTP 49d, range 19-88, CI 44,67-64,97). 7pts were not evaluable (stopped Tx due to s.e). All EGFR+ve pts had disease control (2PR, 1SD). Conclusions: E is a valuable option in elderly NSCLC patients with co-morbidities, especially if they harbor EGFR mutations. Impaired renal function might be associated with propensity to side effects and early Tx discontinuation.

Active Immunotherapy with FavId® (Id/KLH) Following Rituximab Induction: Long-Term Follow-Up of Response Rate Improvement (RRI) and Disease Progression in Follicular Lymphoma Patients (pts).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 691-691 ◽  
Author(s):  
Omer N. Koc ◽  
Charles Redfern ◽  
Peter H. Wiernik ◽  
Fred Rosenfelt ◽  
Jane N. Winter ◽  
...  
Keyword(s):  
Disease Progression ◽  
Median Time ◽  
Response Rate ◽  
Published Data ◽  
Late Response ◽  
Gm Csf ◽  
Best Response ◽  
Long Term Follow Up

Abstract Background: Studies of Id/KLH immunotherapy in treatment naïve (TN) fNHL pts following first remission from chemotherapy have demonstrated a prolonged duration of remission. We expanded this approach in a PhII trial to include TN and relapsed/refractory (R/R) pts with stable disease (SD) or PR or CR/CRu following 4 wkly doses of rituximab. We report here long term follow up of RRI, defined as the % of pts who converted from SD to PR or PR to CR/CRu following initiation of Id/KLH treatment, and analysis of disease progression. Treatment: Pts received rituximab (375mg/m2 i.v. wkly x 4 during wk1–4) and those with stable or responsive disease received Id/KLH (1 mg s.q. mo x 6) starting on wk 12 along with GM-CSF (250 mcg, s.q.) on days 1–4. Pts continued to receive booster injections on a reduced schedule until disease progression. Radiological scans, performed every 3 mos, were reviewed centrally. Disease progression and response were assessed using modified Cheson criteria. This data analysis was performed 32 mo from end of enrollment. Results: 103 pts were enrolled and received rituximab; 89 pts had ≥SD and received Id/KLH + GM-CSF of whom, 54 were R/R, and 35 were TN. The overall response rate (ORR) was 47% (42/89) at mo 3. After the initiation of Id/KLH dosing, ORR improved to 63% (56/89). In RRI pts, median time to best response was 9.1 mos from start of rituximab treatment (5.2 – 29.6 mos). 12 of 39 PR pts (31%) converted to CR/Cru. 14 of 43 SD pts (33%) converted to PR. Pt Groups # of Pts % Prog Free Median TTP Est by K-M (mo) Pts w/RRI 26 69% 37.9 TN rituximab responders 23 70% Not Reached (NR) Rituximab responders (All) 42 60% NR Non Responders (All) 47 36% 14.9 All Pts 89 47% 18.2 TN Pts (All) 35 66% NR Relapsed Pts (All) 54 37% 16.8 Conclusion: RRI following FavId is seen in nearly one third of pts. The magnitude of this improvement, the number of conversions to CR/CRu and median time to best response (9 mo and as late as 29.6 mo) suggests this is likely to be a FavId effect rather than late response to rituximab. Responders and TN pts show more durable responses compared to previously published data for rituximab therapy. FavId may also confer a benefit for nonresponders and R/R pts relative to rituximab alone. To confirm benefit of FavId following rituximab induction, a placebo controlled PhIII study was initiated; it completed enrollment in Jan 06. RRI data from this study is expected to be available in Nov 06.

Liposomal Doxorubicin (Myocet®) Enhance the Efficacy of Bortezomib, Dexamethasone Plus Thalidomide in Refractory Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5087-5087 ◽  
Author(s):  
Stefania Ciolli ◽  
Franco Leoni ◽  
Cinzia Casini ◽  
Carla Breschi ◽  
Alberto Bosi
Keyword(s):  
Median Time ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Single Agent ◽  
Haematological Toxicity ◽  
Comparable Efficacy ◽  
Eligibility Criteria ◽  
Best Response

Abstract Bortezomib (Velcade®) is effective in MM as single agent. A strong rationale supports the association of bortezomib with anthracyclines. Bortezomib may increase the activity of anthracyclines by inhibiting maturation of P-gp, suppressing DNA repair and inducing phosphorylation and cleavage of Bcl-2. Anthracyclines down-regulate the bortezomib anti-apoptotic effect. In vitro studies demonstrated that liposome encapsulated doxorubicin can overcome MDR-1 overexpression. It has a longer half-life, lower cardiac toxicity and comparable efficacy. Thus, we added non-pegylate liposomal doxorubicin (Myocet®) to the low dose VTD regimen (Ciolli et al. Leukemia & Lymphoma2006;47(1): 171–173). Aims of the study were to evaluate the feasibility of treatment and stem cells harvest and transplantation, to compare ORR and TTP in respect to LD-VTD. The study was performed in accordance with the Declaration of Helsinki. Eligibility criteria: pts primary refractory (PR) or relapsed and refractory (R/R), with a LVEF more than 45% and a measurable disease. Therapy: bortezomib 1.0 mg/m2 i.v. bolus days 1, 4, 8 and 11 of a 28-d cycle, Myocet 50 mg/m2 i.v over 60 minutes on day 4 (1 hour after bortezomib), oral dexamethasone 24 mg on the day of and the day following each bortezomib dose. Thalidomide 100 mg/d if non controindicated. All toxicities were defined according to NCI criteria. Response was evaluated after each cycle. Pts with progressive disease (PD) were removed from the study, the others continued until best response for a maximum of 4 cycles. Time to response was from the date of the first administration of bortezomib to the first evidence of response. From June 2005, 28 pts, median age 68 years, entered the study: 5 stage IIA, 20 IIIA and 3 IIIB. 16 (57%) were the PR pts and 12(43%) those R/R. 8(29%) had a β2microglobulin &gt;4 mg/L, 7 a PS &gt;2 and 8 a pre-existing peripheral neuropathy (PN) grade 2. Median time from diagnosis was 4 years and a median of 4 (range 2–6) were the prior therapy lines. All pts had previously received thalidomide plus dexamethasone; 8 had previously received bortezomib. 13 (46%) did not receive thalidomide due to a pre-existing neurological toxicity. Haematological toxicity was registered 14–17 days from the start of therapy and lasted for a maximum of 4 days: grade 2 neutropenia in 3 pts, grade 4 thrombocytopenia in 5. A patient had a grade 4 gastric haemorrhage. 3 pts had pneumonia, 2 HZ infection and 1 a DVT. Other adverse advents of grade &gt;1 were fatigue (50%), nausea (60%), diarrhoea (15%), alopecia (10%). None progression of PN was observed. No patient experienced clinical evidence of cardiac toxicity. At July 31th 2006,. all pts were valuable for response: 3 PD, 4 SD, 21 responders: 8 CR, 2 nCR, 7 PR,4 MR (ORR 75%). Median time to best response was 1 month (range 1– 2). 3 pts successfully harvested the PBSC and 1 was transplanted. After a median follow-up of 9 months, median TTP and OS had not been reached, 23 pts were alive and 5 (2 PD and 3 responders) had died. Myocet did not add toxicity to LD-VTD. PBSC has been successfully performed in eligible pts. More pts and an adequate follow-up are needed to draw any definitive conclusion about TTP and OS, however, this regimen appears feasible and effective with an increased ORR compared to our previous LD-VTD experience (75% vs 53%).

scholarly journals RARE-42. INCIDENCE AND BEHAVIOR OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN PATIENTS WITH HODGKIN’S LYMPHOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi230-vi230
Author(s):  
Carlos Eduardo Silva Correia ◽  
Rachna Malani ◽  
Lisa DeAngelis ◽  
Alison Moskowitz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Median Time ◽  
Hodgkin’S Lymphoma ◽  
Systemic Disease ◽  
Hodgkin's Lymphoma ◽  
Leptomeningeal Disease ◽  
High Dose ◽  
Cns Involvement ◽  
Cns Disease

Abstract INTRODUCTION Central nervous system (CNS) involvement from Hodgkin’s Lymphoma (HL) is rare, with a reported incidence of 0.07–0.5%. There is a paucity of data regarding its natural history and management. METHODS In this retrospective single-institution review, we analyzed all adult patients with HL for CNS involvement (parenchymal or meningeal), who were evaluated at Memorial Sloan Kettering Cancer Center from January 2008 until December 2018. RESULTS A total of 3478 patients with HL were identified, and CNS involvement was found in 10 patients (0.3%). All patients were symptomatic from CNS disease. Four patients had a synchronous presentation. The other 6 patients had a median time from systemic diagnosis to CNS involvement of 8 years (2.5–14). Two patients had radiographic evidence of leptomeningeal disease, however 4 had positive cerebrospinal fluid (CSF) cytology. At time of CNS involvement, 2 patients had confirmed transformation to Non-Hodgkin-Lymphoma on biopsy. 2 patients had EBV-positive HL. One patient died before treatment. Five patients received high-dose methotrexate (HD-MTX) for CNS disease. Of these patients, 1 died during treatment, 2 had partial responses, and 2 had complete response of both systemic and CNS disease; to date they are in remission. Three patients had varied responses to immunotherapy and cytotoxic chemotherapy. Removal of an immunosuppressive agent resolved disease in one EBV-positive patient. Median overall survival (OS) from diagnosis of HL was 10.6 years (1.1–21.2), and OS from time to CNS involvement was 6 years (0.2–15). CONCLUSION The median time from diagnosis to CNS involvement, and OS from time of CNS involvement are higher than previously reported, which may be related to newer therapies for systemic disease. Neuroimaging should be used in conjunction with CSF for diagnostic accuracy. HD-MTX can be used to treat CNS and refractory systemic disease, as historically used for the latter.

scholarly journals Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real-World Clinical Practice: Data from a Belgian Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1744-1744 ◽  
Author(s):  
Timothy Devos ◽  
Koen Theunissen ◽  
Fleur Samantha Benghiat ◽  
Alain Gadisseur ◽  
Stef Meers ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Median Time ◽  
Real World ◽  
Research Funding ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Best Response ◽  
History Of ◽  
T315i Mutation

Abstract Background Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for adult patients with resistant or intolerant chronic phase (CP), accelerated phase, or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), or those with the T315I mutation. In Belgium, ponatinib has been commercially available since March 2016. The goal of this registry was to collect efficacy and safety data in CML and Ph+ ALL patients and to evaluate ponatinib in routine clinical practice in Belgium. Methods This ongoing, prospective, multi-center registry includes patients ≥18 years of age with CML or Ph+ ALL, who have initiated ponatinib treatment. Demographic, efficacy and safety data were collected for patients enrolled from March 2016 (day 0) onwards. Results up to study month 24 are presented. Data were analyzed by descriptive statistics. Ethics Committee approval was obtained and all patients provided informed consent. Results At time of data analysis, 34 patients (21 CP-CML and 13 Ph+ ALL) were enrolled. The median age of CP-CML and Ph+ ALL patients was 57 and 55 years, respectively. Patients were heavily pretreated: 90% of CML and 92% of Ph+ ALL patients had received ≥2 prior TKIs. Several patients had one or more risk factors for TKI cardiovascular toxicity: hypertension (10), history of cardiovascular disease (11), smoker (10), hypercholesterolemia (5), and diabetes (4). Median follow-up was 539 days for CML and 135 days for Ph+ ALL patients. The reasons for starting ponatinib therapy were related to refractoriness to previous TKIs (36%), progression (18%), presence of the T315I mutation (18%) or intolerance (29%). Eighty percent (8/10) of the patients who started ponatinib due to intolerance to previous TKIs had received ≥3 prior TKIs. At entry, 17 of the 34 patients (50%) had a confirmed BCR-ABL mutation. Of these 17, 10 (59%; 5 CML and 5 Ph+ ALL) had the T315I mutation. Starting doses of ponatinib in CML patients were 45 mg (76%), 30 mg (10%) and 15 mg (14%) once daily. Starting doses in Ph+ ALL patients were 45 mg (85%), 30 mg (8%) and 15 mg (8%). At latest follow up, the median treatment duration for the 21 CML patients was 531 days (range 15 - 2483) and for the 13 Ph+ ALL patients it was 123 days (range 13 - 1945). Best response was a major molecular response (MMR), which was obtained in 71% of CML patients and 38% of Ph+ ALL patients. The median time-to-best response was 175 days in CML and 35 days in Ph+ ALL patients. In the 10 patients (7 CML and 3 Ph+ ALL) who started ponatinib because of intolerance to several previous TKIs, 80% achieved MMR. The median time to achieve best response in these patients was 192 days for CML and 31 days for Ph+ ALL patients. Treatment-related adverse events (AEs) were reported in 20 patients (59%); the most common were rash (26%), dry skin (9%) and constipation (9%). Three patients reported ≥1 treatment-related serious AE (SAE): thrombocytopenia (n=1), cholecystitis (n=1) and hepatocellular injury (n=1). Three serious cardiovascular events were observed in 1 patient, who had a history of congenital cardiomyopathy and aortic prosthesis. They were scored as not related to ponatinib. Dose reductions or interruptions occurred in 33 cases (20 in CML and 13 in Ph+ ALL patients), with the following reasons most frequently mentioned: AEs (76%), to prevent AEs (18%) and other (6%). Dose increases occurred in 12 cases (10 in CML and 2 in Ph+ ALL patients), for the following reasons: good tolerance of treatment (58%), no or low response (33%) or other (8%). At time of analysis, 19 patients (9 CML and 10 Ph+ ALL) had discontinued treatment, of which 32% due to AEs, 5% due to an SAE, 21% due to planned allogeneic transplant, 16% due to disease progression and 26% due to other reasons. [Note: Percentages may not total 100 due to rounding] Conclusion Real-world evidence from this Belgian registry shows that ponatinib has a favorable efficacy and safety profile in, and supports its use in CML and Ph+ ALL patients who are resistant or intolerant to previous therapies or those with the T315I mutation. Deep molecular responses were obtained in the majority of patients. No new safety signals emerged with ponatinib treatment than those previously reported. Funding: Incyte Biosciences Benelux BV Disclosures Devos: Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Theunissen:Incyte: Honoraria. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Kuipers:Incyte Biosciences Benelux BV: Employment.

scholarly journals Dexamethasone, Rituximab and Cyclophosphamide (DRC) As Salvage Therapy for Waldenstrom Macroglobulinemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2972-2972 ◽  
Author(s):  
Jonas Paludo ◽  
Jithma P Abeykoon ◽  
Amanda Shreders ◽  
Sikander Ailawadhi ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
International Workshop ◽  
Time To Event ◽  
Advisory Committees ◽  
Incurable Cancer ◽  
Mutation Status ◽  
Best Response

Abstract Background WM remains an incurable cancer despite recent advances. While a phase II trial has demonstrated efficacy of dexamethasone, rituximab and cyclophosphamide (DRC) in the treatment-naïve (TN) patients, this regimen has not been studied systematically in the relapsed/refractory (R/R) setting. Recent data has suggested the MYD88mutation status in WM patients can serve as a predictive marker with therapies such as ibrutinib. We examined the efficacy and tolerability of up to 6 cycles of DRC, with focus on R/R population and activity of this regimen with respect to the patients' MYD88L265Pstatus. Methods Records of WM patients seen consecutively at Mayo Clinic campuses in Rochester, Arizona and Florida from 01/2007 to 12/2014 were reviewed. MYD88L265P status, as assessed by AS-PCR, was recorded when available. Data obtained from symptomatic patients treated with DRC (dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5) were analyzed. Time-to-event analyses were performed from DRC therapy using the Kaplan-Meier method. We used the Consensus response criteria (6th International Workshop). Results Of 100 symptomatic patients who received DRC, 50 had R/R WM (40% refractory) and 50 were TN. Table 1 shows the patients' baseline characteristics. In the R/R population, DRC was 2nd line (range 2-8) therapy in 58% of patients. The median IgM levels declined from 3,870 mg/dL to 1,846 mg/dL (p=0.0001) at best response. Median follow-up from DRC was 51 months (95% CI: 38-55). The median time-to-best response was 6.8 (0.5-28) months. Overall response rate (ORR) was 87% [VGPR 4%, PR 64%, MR 19%]. Four patients (9%) achieved SD and 2 patients (4%) had PD. Of the sixteen deaths (32%) noted at time of analysis, 11 were related to progressive disease. The median disease-specific survival (DSS) from DRC was not reached (NR) (95% CI: NR-NR). The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 months (95% CI: 15-51) and 50 months (95% CI: 35-60), respectively. In contrast, in the TN patients the median IgM levels declined from 4,130 mg/dL to 1,250 mg/dL (p=0.0001) at best response; median time to best response was 11 (0.6-47) months; median follow-up from DRC was 30 months (95% CI: 21-36). ORR was 96% [VGPR 17% (n=8), PR 70% (n=32), MR 9% (n=4)]. Of the 7 deaths (14%) at time of analysis, 4 were related to WM progression. Median DSS from DRC was NR (95% CI: NR-NR); median PFS and TTNT were 34 months (95% CI: 23-NR) and NR (95% CI: 37-NR), respectively. Among 29 genotyped patients in whom MYD88 mutation status was available, MYD88L265P was present in 25 patients (8 of 10 TN and 17 of 19 R/R patients). The response rates and the time-to-event outcomes were similar in the MYD88L265P and wild-type patients. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Conclusions Similar to the frontline setting, DRC is an active and well-tolerated salvage regimen. In contrast to ibrutinib, DRC offers a less expensive, limited-duration treatment option, with preliminary data suggesting activity independent of patients' MYD88 mutation status. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Kumar:Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Kesios: Consultancy; Array BioPharma: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy. Dispenzieri:Jannsen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; pfizer: Research Funding; Celgene: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Alnylam: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Ansell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Kapoor:Amgen: Research Funding; Celgene: Research Funding; Takeda: Research Funding.

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