Prospective observational trial of low-dose skin electron therapy in mycosis fungoides using rotational technique.

e22077 Background: Low dose total skin electron therapy (TSET) utilizing 12 Gy in 12 fractions has been shown to provide a durable treatment response for dermal lesions caused by mycosis fungoides secondary to cutaneous T cell lymphoma (CTCL). We sought to prospectively assess the durability of response and quality of life (QOL) for patients receiving low dose TSET using the rotational technique technique. Methods: We prospectively enrolled patients with CTCL on an IRB approved study from 2016 to 2019 who had pathologically confirmed CTCL from stage IB-III. Patients completed a baseline validated Skindex-29 survey encompassing 29 questions assessing QOL. Physicians graded the appearance of the skin using the modified severity-weighted assessment tool (mSWAT) at baseline. Patients received 12 Gy in 12 Fractions on consecutive dates and patients were treated with a dual field rotational technique. The mSWAT was reassessed on ensuing follow-up visits along with the Skindex. The primary outcome was overall response rate with the secondary outcomes being time to treatment response, duration of clinical benefit (time to requiring an additional intervention), as well as improvements in Skindex questionnaire items. Results: We enrolled 20 patients and recorded an overall response rate (ORR) of 90% with four complete responses. The time to treatment response was 9.7 weeks. While the baseline mSWAT was 55.6 it declined to a median mSWAT of 2.2 at last follow-up (p < 0.001) with there being a median decline of nearly 97% in the scores. The median duration of clinical benefit was 15.7 months. There was a precipitous decline in the Skindex total score and every subdomain when comparing each follow-up visit (p = 0.004) with post-hoc analysis demonstrating the decline between the baseline visit and first follow-up as the primary driver of the decline (p < 0.0001). Conclusions: This prospective study demonstrates the subjective and objective clinical benefits of utilizing low dose TSE with a dual beam rotational technique. This control rates and QOL will continue to be observed for ongoing feasibility as a treatment modality.

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Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.

Blood ◽

10.1182/blood.v106.11.2522.2522 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2522-2522 ◽

Cited By ~ 3

Author(s):

Hagop Kantarjian ◽

Susan O’Brien ◽

Francis Giles ◽

Farhad Ravandi-Kashani ◽

Stefan Faderl ◽

...

Keyword(s):

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

Optimal Schedule ◽

Dose Schedule ◽

Overall Response ◽

Transfusion Independence ◽

Secondary Mds ◽

To Receive

Abstract Background Decitabine (DAC), a hypomethylating agent, has shown activity in MDS. DAC 150 mg/m2 by continuous infusion has been associated with CR rates of 10% to 20%. We investigated optimizing the dose schedule of DAC in MDS. Study Group and Methods Patients (pts) with IPSS intermediate 1–2 & high risk MDS were randomized to one of 3 schedules of DAC: 1) 20 mg/m2 IV over 1 hour daily x 5; 2) 10 mg/m2 IV over 1 hour daily x 10; or 3)10 mg/m2 subcutaneously (SQ) BID x 5. A total of 95 pts are to be treated; Bayesian randomization is implemented based on CR rates. Courses were given every 28 days. Delays to allow counts recovery were permitted every 3 courses, or if myelosuppression without disease, or severe myelosuppression complications. Pts were allowed to receive erythropoietin 40,000 units weekly for anemia, or GCSF if needed. Response criteria for CR & PR were as for AML (PR requiring also ↓ blasts by >50%). Clinical benefit (CB) referred to one or more of: platelets î by ≥ 50% and >30 x 109/L, or granulocytes increase by ≥ 100% and to >109/L, or hemoglobin î by ≥ 2 g/dl or transfusion independence, or splenomegaly ↓ by 50% or more, or monocytes ↓ by 50% or more (pretreatment >5 x 109/L). Results 92 pts have been treated; median age 65 (31–90) yrs; 66% >60 yrs old. IPSS: intermediate-1 25%; intermediate-2 38%; high 19%; CMML 17% Cytogenetic abnormalities 57%; secondary MDS 17%; marrow blasts > 10% in 31%. 27 pts had prior erythropoietin; 17 had prior GCSF; 22 had other prior therapies. Presently, 89 pts have received 1 course. Results: 32 CR (36%); 7 PR (8%); 13 marrow CR + CB (15%); 16 CB (18%); overall response 68/89=76%. Median courses to CR 3 (range 1 to 6). Median follow-up of 9 months; 48 pts continue on DAC. Compared with a 114 pts with MDS who received intensive chemotherapy (2000–2004), CR rate was lower with DAC (36% vs. 45%), overall response rate was favorable; 6-week mortality was lower with DAC (1% vs. 21%); and estimated survival favorable (p = 0.00007). CR rates by schedule: 5 days IV 24/58 (41%); 5 days SQ 4/14 (28%); 10 day IV 4/17 (24%). There was more myelosuppression with 10 day IV. After 55 patients were randomized, the 5 day IV arm was determined statistically superior, therefore, remaining patients were not randomized, but were treated with 5 days IV therapy. Conclusions DAC has significant anti-MDS activity; 2) optimal schedule: 20 mg/m2 IV over 1 hour daily x 5; 3) timely repeated courses needed for optimal response.

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Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study

Journal of Clinical Oncology ◽

10.1200/jco.19.01056 ◽

2020 ◽

Vol 38 (1) ◽

pp. 20-28 ◽

Cited By ~ 38

Author(s):

Michael S. Khodadoust ◽

Alain H. Rook ◽

Pierluigi Porcu ◽

Francine Foss ◽

Alison J. Moskowitz ◽

...

Keyword(s):

Mycosis Fungoides ◽

Phase Ii ◽

Overall Response Rate ◽

Response Rate ◽

Treatment Discontinuation ◽

Sézary Syndrome ◽

Overall Response ◽

Multicenter Phase ◽

Flare Reaction

PURPOSE To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS). PATIENTS AND METHODS CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria. RESULTS Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature. CONCLUSION Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

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Real-world experience of talimogene laherparepvec in patients receiving immunotherapy in metastatic melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22003 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22003-e22003

Author(s):

Tapas Ranjan Behera ◽

Jung Min Song ◽

Jennifer S. Ko ◽

Michael J. McNamara ◽

Pauline Funchain ◽

...

Keyword(s):

Clinical Trials ◽

Metastatic Melanoma ◽

Treatment Response ◽

Median Time ◽

Real World ◽

Overall Response Rate ◽

Response Rate ◽

Talimogene Laherparepvec ◽

Overall Response

e22003 Background: Talimogene laherparepvec (TVEC) is an oncolytic herpes virus approved by the FDA for intralesional therapy in unresectable metastatic melanoma. However, little is known regarding the effectiveness of TVEC+checkpoint inhibition (CPI) outside of clinical trials. We present outcomes of the largest single institution experience with TVEC in the context of different immune checkpoint inhibitors. Methods: All patients with stage III-IV unresectable melanoma having received TVEC were evaluated. Patient demographics, clinicopathological characteristics, TVEC treatment response and outcomes were assessed. Final analysis included those who received TVEC adjacent to CPI with a minimum 6-month follow-up, excluding patients on clinical trials. Response was estimated by sequential measurement of injectable on-target lesions. Results: A total of 62 patients received TVEC from 2016 to 2019, of which 43 remained excluding Merkel cell carcinoma, patients on trials, and TVEC monotherapy. Of 30 patients with available treatment response data and at least 6-months follow-up, median age was 68.5 years (30-99 years), 40% were female, 16 (53.3%) stage IV. Median follow-up was 17.5 months (6-43 months). At 6 months, 20 (67.7%) patients were alive; at 1 year, 17 (56.7%) patients were alive. Eighteen patients received pembrolizumab, 7 nivolumab and 5 ipilimumab/nivolumab. Median number of TVEC doses received was 8 (3-31 doses). Median time on TVEC therapy was 4 months (1-26 months). Overall response rate for on-target lesions was 24 (80%), with complete local response (CR) in 15 (50%), partial response (PR) in 9 (30%), and progressive disease (PD) in 6 (20%). Median time to response was 6 weeks (2-17 weeks); 5 in CR, 6.5 in PR and 5.5 in PD groups. Adverse events were mostly mild and limited to constitutional symptoms. Conclusions: To our knowledge this is the largest real-world experience assessing TVEC in patients receiving CPI. Local overall response rate appears higher in comparison to historic numbers for TVEC monotherapy. The findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma and has robust outcomes in real-life clinical settings.

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Survival Benefits of Patients with Non-Hodgkin’s Lymphoma Treated with Rituximab Combined with Chemotherapy.

Blood ◽

10.1182/blood.v104.11.4625.4625 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4625-4625

Author(s):

Zhixiang Shen ◽

Junmin Li ◽

Aihua Wang ◽

Yu Chen

Keyword(s):

B Cell ◽

Overall Response Rate ◽

Response Rate ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Overall Response ◽

Large B Cell

Abstract Purpose: Rituximab combined with chemotherapy has been recommended as first-line or second-line standard regimen in most subtypes of B-cell lymphoma in China by the 2004 National Comprehensive Cancer Network lymphoma therapy guideline. We have conducted a multicenter trial to evaluate the efficacy and safety of rituximab in combination with standard chemotherapy (CHOP) in patients with previously untreated or relapsed indolent and aggressive NHL. Methods: Patients received 4–8 cycles of rituximab plus CHOP every 21 days. For each cycle, rituximab (375mg/m2) was given on day 1 and CHOP started on day 3. CHOP consisted of cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2mg/dose) given intravenously on day 3, and oral prednisone 100mg on days 3–7. Results: A total of 221 patients were enrolled on the trial, 128 males and 93 females with a mean age of 49 years (range 10–83 years). The main lymphoma subtypes were small lymphocytic (15 patients, 7%), follicular (27 patients, 12%), and diffuse large B-cell (160 patients, 72%). In total, 56 patients had indolent NHL and 165 aggressive NHL. The overall response rate for all patients was 86% with 57% complete responses. In patients with indolent NHL the overall and complete response rates were 95% and 55% respectively. After a median 12 months follow up, progression-free survival in patients with indolent NHL was 88%±5% at 1 year and 83%±6% at 2 years. In the 160 patients with diffuse large B-cell lymphoma, the overall response rate was 88% with 61% complete responses, and after a mean follow-up of 6 months, predicted 1-year and 2-year progression-free survival were 88%±5% and 83%±7% respectively. Infusion-related adverse events occurred in 4% of patients, associated with the first infusion of rituximab. Subanalyses according to subtype, stage, IPI and other factors will be presented. Conclusion: Rituximab plus chemotherapy is an effective, well-tolerated treatment that achieves high response rates and long progression-free survival in both indolent and aggressive NHL.

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A Phase I/II Trial of Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3542.3542 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3542-3542 ◽

Cited By ~ 6

Author(s):

Rakesh Popat ◽

Catherine Williams ◽

Mark Cook ◽

Charles Craddock ◽

Supratik Basu ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase I ◽

Median Time ◽

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

Chemotherapeutic Agents ◽

Time To Progression ◽

Overall Response ◽

Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (MR+PR+CR) of 46% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were classified by EBMT criteria. Results: To date 39 patients have been enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. 36 have now completed at least 1 cycle and are therefore evaluable for response. The overall response rate (CR+PR+MR) across all treatment levels was 75% rising to 81% (CR 11%; nCR 3%; VGPR 8%; PR 39%; MR 19%) with the addition of dexamethasone in 13 cases for suboptimal response. Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression is 10.1 months and the median overall survival has not yet been reached at a median follow-up of 7.4 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 13 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma where a response rate of 81% is seen with 14% achieving nCR/CR. The toxicity profile associated is predictable, manageable and predominantly haematological. Recruitment is ongoing to a total of 53 patients.

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Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma: Final Results of a Phase I/II Clinical Trial.

Blood ◽

10.1182/blood.v110.11.2713.2713 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2713-2713

Author(s):

Rakesh Popat ◽

Catherine Williams ◽

Mark Cook ◽

Charles Craddock ◽

Supratik Basu ◽

...

Keyword(s):

Clinical Trial ◽

Multiple Myeloma ◽

Phase I ◽

Median Time ◽

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

Time To Progression ◽

Overall Response ◽

Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (≥PR) of 43% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were defined by EBMT criteria. Results: 53 patients were enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. The overall response rate (≥PR) across all treatment levels (n=52) was 65% rising to 69% (CR 19%; nCR 4%; VGPR 6%; PR 40%; MR 15%) with the addition of dexamethasone in 27 cases for suboptimal response. Of the 32 patients treated at the MTD the overall response rate (≥PR) was 78% (CR 28%; nCR 6%; VGPR 6%; PR 38%; MR 9%). Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression was 10 months and the median overall survival has not yet been reached at a median follow-up of 17 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 19 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma with a response rate (≥PR) at the MTD of 78% including 34% nCR/CR. The toxicity profile is predominantly haematological.

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Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Blood ◽

10.1182/blood-2019-126441 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5020-5020

Author(s):

Wenrui Yang ◽

Bing Han ◽

Hong Chang ◽

Bingyi Wu ◽

Fankai Meng ◽

...

Keyword(s):

Aplastic Anemia ◽

Real World ◽

Overall Response Rate ◽

Response Rate ◽

Line Treatment ◽

First Line ◽

Overall Response ◽

Treatment Naïve ◽

First Line Treatment

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

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First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study

Journal of Clinical Oncology ◽

10.1200/jco.21.01015 ◽

2021 ◽

Author(s):

Heinz-Josef Lenz ◽

Eric Van Cutsem ◽

Maria Luisa Limon ◽

Ka Yeung Mark Wong ◽

Alain Hendlisz ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Mismatch Repair ◽

Clinical Benefit ◽

Objective Response Rate ◽

Low Dose ◽

Response Rate ◽

Objective Response ◽

First Line

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

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Antigenic Variation of Hairy Cell Leukemia Defines a CD25 Negative Variant with a Uniform Immunophenotype and Distinct Clinicopathologic Features.

Blood ◽

10.1182/blood.v104.11.1102.1102 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1102-1102

Author(s):

Henry Y. Dong

Keyword(s):

Flow Cytometry ◽

Hairy Cell Leukemia ◽

Standard Therapy ◽

Overall Response Rate ◽

Response Rate ◽

Complete Response ◽

Hairy Cell ◽

Cell Leukemia ◽

Overall Response

Abstract Classical hairy cell leukemia (HCL) coexpressing both CD25 and CD103 is highly responsive to the treatment with cladribine and pentostatin (complete response rate, 75–95%; overall response rate, 86–100%). HCL variant in the literature is characterized by HCL-like morphology, lack of CD25 coexpression, and variable immunophenotypes indistinguishable from those of splenic marginal zone B cell lymphoma (Matutes, et al. Leukemia2001; 15:184). Importantly, HCL variant is associated with a poor response to standard therapy. It is unclear if HCL cases lacking CD25 but otherwise phenotypically identical to classical HCL belong to HCL or HCL variant, and if the standard therapy is effective in these patients. To further delineate features of HCL and its variants, we analyzed immunophenotyping data, by flow cytometry or immunohistochemistry, or by both when feasible, in 260 consecutive patients with HCL (Dong, et al. Mod Pathol2003; 16:230A). The diagnosis was established by hairy cell morphology together with coexpression of strong CD20 and CD22, bright CD11c, and CD103. Clinical data were obtained for a subset of cases in which expression of CD25 was distinctly absent. Our results were consistent with the literature in that HCL has a consistent and unique immunophenotypic profile, which allowed detection of residual HCL by flow cytometry at levels as low as 0.1% of total cells. In addition, approximately 20% and 37% of classical HCL coexpressed CD10 and BCL-1 respectively, which may significantly confuse the diagnosis in an incomplete work-up. Interestingly, there were 43 cases (20% of all CD103+ cases) that lacked CD25 but were otherwise identical to classical HCL in their uniform phenotypic profiles. Compared with classical HCL, patients with the CD25- HCL were generally older (medium age: 59yrs vs. 79yrs; p=0.001) and frequently had leukocytosis (medium WBC: 3.0x109/L vs. 24.5x109/L; p=0.014). Among 14 patients with follow up data, 7 were treated with cladribine or pentostatin. The complete response (CR) rate was 14.3% (1/7) and the overall response rate was 57.1% (4/7). Three patients had no response. One patient who had an initial partial response (PR) to pentostatin died of the disease 10 months after the diagnosis. Of others, an additional two patients achieved CR and PR upon initial treatment with fludarabine and Rituxamab respectively. Four patients were untreated and were alive with disease (follow up, 21–41 months). One patient died of the disease in 2 years and treatment for this patient was unknown. These clinical features overlapped with those of HCL variant in the literature. However, unlike the HCL variant that has significant phenotypic heterogeneity, including lack of CD11c and CD103 in a substantial number of cases, the CD25- HCL was remarkably uniform in phenotype and can be easily identified by immunophenotyping. In conclusion, these results suggest that lack of CD25 in HCL defines a clinically distinct chronic lymphoproliferative disorder, which appears to require different clinical management.

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A Case Series Of Continuous Low Dose Lenalidomide In Patients With Relapsed Or Refractory Classical Hodgkin Lymphoma

Blood ◽

10.1182/blood.v122.21.5134.5134 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5134-5134 ◽

Cited By ~ 1

Author(s):

Ahmed Sawas ◽

Sean Clark-Garvey ◽

Ellen Neylon ◽

Ameet Narwal ◽

Kathleen Maignan ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Dose Reduction ◽

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

Median Number ◽

Classical Hodgkin Lymphoma ◽

Time To Progression ◽

Overall Response

Abstract Background Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge with limited effective treatments after high dose therapy with autologous stem cell transplantation (ASCT). Lenalidomide (Revlimid®) is an approved anti-neoplastic therapy for multiple myeloma, mantle cell lymphoma and myelodysplastic syndrome with del(5q). It has emerged as an agent with a manageable toxicity profile and promising clinical activity in a number of B cell malignancies. Two clinical trials have evaluated lenalidomide in rel/ref patients with cHL at a dose of 25mg daily for 21 days of a 28 day cycle. One study reported an overall response rate of 14%, a median time to progression of 3.2 month, with a median number of prior therapies of 2. The second study reported an overall response rate of 19%, a cytostatic response rate (CR+PR+SD> 6 month) of 33%, with a median number of prior therapies of 4. The most common reported grade 3-4 side effects in these studies respectively were: neutropenia 28% and 47%, thrombocytopenia 28% and 27%, and anemia 21% and 27%. We report on our experience in this case series with continuous low dose (10-20mg) lenalidomide in rel/ref cHL patients. Methods Twelve rel/ref cHL patients (pts) who previously underwent (or were not candidates for) ASCT and/or clinical trials were administered a daily dose of lenalidomide. Pts received 10mg and were titrated up to 20mg, if tolerated, with continuous dosing for 30 day cycles. Treatment continued until disease progression or the development of unacceptable adverse event at the lowest administered dose (5mg) of lenalidomide. Results The median age at treatment was 33 (range 24-61) years with 5 females. Median number of prior therapies was 8 (range 3-16). Ten pts had received a prior stem cell transplant (9 ASCT, 1 allogenic, and 1 both ASCT and allogeneic). Of the 12 pts, we observed 3 PR (25%), and 9 SD (8 for more than 6 months) for an overall response rate of 25% and an overall cytostatic response rate (CR+PR+SD> 6 month) of 92%. Median number of cycles received was 6 (range 2-15); six patients remain on therapy. One patient with a PR after 2 cycles of therapy underwent allogeneic stem cell transplant. The median time to progression for the remaining 11 patients was 7.5 months (range 4-15 months). Three patients had progression of disease, all of whom were able to enroll on clinical trials. One patient discontinued therapy because of exacerbation of preexisting neuropathy and was able to transition to chemotherapy. A second patient discontinued therapy after experiencing significant fatigue. In general, the treatment was well tolerated, and the most common clinically significant adverse events were: neutropenia in 4 patients which was managed by GCSF support and dose reduction, exacerbation of neuropathy in 2 patients with one patient discontinuing therapy and dose reduction in the second, and diarrhea in one patient managed with dose reduction. Conclusions Despite a far more heavily treated patient population, continuous, low dose, single agent lenalidomide was both tolerable and effective in patients with rel/ref cHL. Continuous low dose lenalidomide is able to provide meaningful time to progression and bridge to further therapy. A clinical trial to evaluate the efficacy of continuous daily dosing of lenalidomide in rel/ref cHL is warranted. Disclosures: Off Label Use: Lenalidomide in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma. O'Connor:Celgene: Consultancy, Research Funding.

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