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May 31, 2020 - 08:05 pm Posted in ASCO and ASH Posted in ASCO Conference Coverage Posted in Breast Posted in Lymphoma (includes NHL, HL, CNS Lymphoma) Posted in Melanoma (includes BCC) Posted in Multiple Myeloma comments0 Comments

Sunday’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting featured late-breaking data from a phase 3 trial evaluating early local therapy in metastatic breast cancer and the results of the phase 3 ENDURANCE trial.

Other important studies from the meeting were the ALPHA trial, which is evaluating an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy, and the C-144-01 trial, which is evaluating an autologous tumor infiltrating lymphocyte (TIL) therapy.

Early local therapy offers no survival benefit in patients with de novo metastatic breast cancer and an intact primary tumor, according to the results of a phase 3 trial by the ECOG-ACRIN Research Group (Abstract LBA2).

The trial included 256 patients who received optimal systemic therapy before being randomly assigned to either continue optimal systemic therapy (n=131) or receive optimal systemic therapy with locoregional therapy (n=125).

The 3-year overall survival (OS) rate was not different for the locoregional therapy arm compared with the optimal systemic therapy alone arm (68.4% vs 67.9%; P=0.63) and neither was the risk of death (HR=1.09; 90% CI, 0.80 – 1.49).

Although the locoregional therapy arm had a reduced risk of locoregional recurrences/progression compared with the optimal systemic therapy alone arm (HR=0.37; 95% CI, 0.19 – 0.73), no improvements were seen for health-related quality of life (HRQOL). At one timepoint (18 months), HRQOL was significantly worse for the locoregional therapy arm (P=0.001).

“For de novo stage metastatic breast cancer, existing data supports that locoregional therapy does not improve survival and should not be routinely applied in this population,” said study discussant Julia White, MD, professor of radiation oncology at The Ohio State University.

Carfilzomib and Bortezomib Tie for First

The replacement of carfilzomib for bortezomib in a regimen of bortezomib, lenalidomide, and dexamethasone (VRd) did not improve outcomes for patients with newly diagnosed multiple myeloma, results showed in the second interim analysis of the phase 3 ENDURANCE trial (Abstract LBA3).

Patients who received carfilzomib, lenalidomide, and dexamethasone (KRd; n=545) had a similar progression-free survival (PFS; HR=1.04; 95% CI, 0.8 – 1.3; P=0.74) and OS (HR=0.98; 95% CI, 0.71 – 1.36; P=0.92) to those who received VRd (n=542). A higher proportion of particularly good partial responses was seen with KRd compared with VRd (55.5% vs 49.9%).

KRd had a significantly higher rate of cardiac, pulmonary, and renal treatment-related adverse events (16.1% vs 4.8%; P<0.001), while VRd had a significantly higher rate of peripheral neuropathy (53.4% vs 24.4%; P<0.001). No difference in frequency of secondary primary cancers was seen.

Study discussant Jesus Berdeja, MD, director of myeloma research at Sarah Cannon Research Institute, pointed out that KRd costs nearly $16,000 more per cycle than VRd, which totals to a nearly $100,000-difference for 12 cycles.

“In newly diagnosed multiple myeloma without high-risk features, VRd and KRd appear to be equivalent options for frontline treatment,” Dr Berdeja said. “Comorbidities and toxicity profiles should guide the choice between the two regimens in any individual patient.”

ALPHA Trial Debuts Off-the-Shelf CAR T

An off-the-self allogeneic CAR T-cell therapy known as ALLO-501 appeared safe and showed clinical activity in a small group of patients with relapsed or refractory large B-cell or follicular lymphoma, according to data from the single-arm phase 1 ALPHA trial (Abstract 8002).

“Allogeneic CAR T-cell therapy may provide the benefits of autologous CAR T-cell therapy, while also addressing its challenges,” said study presenter Sattva Neelapu, MD, MD Anderson Cancer Center. “It has the potential to treat all eligible patients, the convenience of repeat dosing, and simplifies the logistics of manufacturing.”

Patients received CD19-targeted ALLO-501 at one of three dose levels and, during lymphodepleting chemotherapy, an investigational monoclonal antibody called ALLO-647, which targets CD52. Patients were heavily pretreated (median of 4 prior therapies), and 4 patients previously received autologous CAR T-cell therapy.

About one-third of patients (7 of 22) had cytokine release syndrome, which included only one grade 3 event and no grade 4. Half of patients developed infection, most of which was grade 1 (23%) or 2 (18%). There were no reports of graft-versus-host disease.

At a median follow-up of 3.8 months, 12 of 19 patients (63%) available for efficacy analysis achieved a response, which included 7 complete responses (37%). Nine patients who achieved a response continue to have a response.

Dr. Neelapu said these results suggest that the safety and the short-term efficacy, in terms of the response rates, for this product is “comparable” to autologous CAR-T products that are currently in clinic. “Further follow-up is necessary to determine the durability of those responses.”

C-144-01 Trial Shows Potential of TILs

Autologous TIL therapy lifileucel appeared safe and to have clinical activity in patients with unresectable metastatic melanoma, according to the results of cohort 2 from the phase 2 C-144-01 trial (Abstract 10006).

Lifileucel is an autologous adoptive cell transfer therapy that involves surgically resecting a patient’s tumor and sending it to the manufacturing facility. Tumor infiltrating lymphocytes (TILs) are then obtained from the tumor, expanded, shipped back to clinical sites, and infused into the patient. Patients in cohort 2 (n=66) received lifileucel that was cryopreserved before shipment. Patients also received up to 6 doses of interleukin-2 after infusion to promote expansion of the TILs.

Most patients (97.0%) had grade 3 or 4 treatment-emergent adverse events, with thrombocytopenia (81.8%), anemia (56.1%), febrile neutropenia (54.5%), and neutropenia (39.4%) being the most common. The number of adverse events decreased over time.

Overall, 24 (36.4%) patients achieved a response, which included 2 complete and 22 partial responses. The disease control rate was 80.3%. At a median follow-up of 18.7 months, the median duration of response had not yet been reached (range, 2.2 – 26.9+ months). Responses were seen across subgroups, which include age, PD-L1 status, and BRAF mutation status.

“Notable, observed responses tended to deepen over time,” said study presenter Amod Sarnaik, MD, Moffitt Cancer Center. “These data therefore demonstrate potential efficacy and durability of response in a patient population with severely limited treatment options.”

By Christina Bennett, MS

 

As the 2018 American Society of Hematology (ASH) Annual Meeting continues, we focus on two studies that have the potential to be practice-changing for the treatment of older patients with AML and younger patients with favorable-prognosis diffuse large B-cell lymphoma (DLBCL), the development of a personalized risk stratification model for patients with myelodysplastic syndromes (MDS), and the finding that pre-hematopoietic cell transplant (HCT) microbiota injury is associated with poorer overall survival (OS).

Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies (559)

Results from the Beat AML umbrella study demonstrated that it was feasible to implement a rapid treatment assignment within 7 days or less for 95.8% of elderly patients with AML, reported Amy Burd, PhD, Leukemia and Lymphoma Society.

This precision medicine trial tested the hypothesis that outcomes for patients could be improved by matching them to the increasing number of available targeted therapies. The primary objectives were to determine (1) the feasibility of completing molecular, immunophenotypic, and/or biochemical studies in ≤7 calendar days, (2) the feasibility of assigning patients to sub-studies in the master protocol based on the test results, and (3) the clinical efficacy of novel treatment strategies in each of the sub-studies.

The trial enrolled patients age ≥60 years with previously untreated AML. Treatment was assigned based on the best curative option using molecular profiling results. Median age was 72 years, and 37.9% of patients were age ≥75 years.

So far 365 patients have been enrolled, of whom 285 were assigned treatment; 146 patients received the assigned treatment. Most of the patients who were not treated received other therapies, including standard of care, alternative treatment prior to assignment, or enrollment in an alternative trial after assignment; 7 died during the 7-day period, and 23 opted to enter palliative care.

The trial began with 3 sub-studies, which has since increased to 11 sub-studies, providing more options. Promising efficacy has been seen in several treatment arms, and early death and disease progression prior to treatment assignment is uncommon outside of MLL rearranged AML which progresses rapidly and requires early treatment initiation. Two sub-study updates are being presented at the meeting (abstracts 4053 and 287).

Excellent Outcome of Young Patients (18-60 years) with Favourable-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 4 Cycles CHOP Plus 6 Applications of Rituximab: Results of the 592 Patients of the Flyer Trial of the Dshnhl/GLA (781)

Results of the FLYER trial showed that reducing cycles of CHOP-like chemotherapy from the standard 6 cycles of rituximab (R)-CHOP to 4 cycles of CHOP plus 6 doses of R maintained efficacy and reduced toxicity for younger patients with good prognosis DLBCL.

Viola Poeschel, MD, Department of Hematology, Oncology and Rheumatology, Saarland University Medical School, Homburg/Saar, Germany, presented the results. FLYER enrolled previously untreated patients age 18 to 60 years with stage I/II aggressive B-cell lymphoma, with age-adjusted International Prognostic Index of zero and no bulky disease. Patients were randomly assigned to treatment with 6 cycles or R-CHOP or 4 cycles R-CHOP plus 2 additional cycles of R in 21-day cycles.

The primary endpoint was progression-free survival (PFS). The 36 month PFS was 94% (95% CI 91%-97%) for the 6 x R-CHOP-21 group (n=295), and 96% (95% CI 94%-99%) for the 4 x R-CHOP-21 + 2 x R group (n=293) at a median follow-up of 66 months.

Likewise, the 36-month overall survival (OS) was similar between the treatment groups: 98% (95% CI 96%-99%) in the standard therapy group and 99% (95% CI 98%-100%) in the reduced chemotherapy group at a median follow-up of 67 months.

Fewer hematologic adverse events (AE) were reported in the reduced chemotherapy group, as well as an overall reduction of non-hematologic AEs by approximately one third.

A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes (793)

Current treatment guidelines for MDS are based on risk stratification for progression to AML, and although HCT is potentially curative in high-risk disease, associated toxicities make it inappropriate for low-risk disease. Aziz Nazha, MD, Cleveland Clinic, Cleveland, OH, described the development of a prediction model that uses a machine learning approach to provide a personalized, patient-specific estimate of risk.

Dr. Nazha’s group show that when looking at survival of patients with MDS by Revised International Prognostic Scoring System (IPSS-R) for MDS risk category, outcomes are heterogeneous.

The model was developed using clinical and mutational data from patients with MDS in a combined cohort from the Cleveland Clinic and Munich Leukemia Laboratory (training cohort, n=1471) and validated in a separate cohort (validation cohort, n=831) from the Moffitt Cancer Center. Forty gene mutations commonly occurring in myeloid malignancies were sequenced. Patients undergoing HCT were censored at the time of transplant. An algorithm was used to build the model that randomly selected clinical and molecular variables to determine survival. Variables were ranked from the most to the least important for OS.

A clinic-friendly web application tool has been built from the final model, allowing input of important risk factors to calculate predicted OS for individual patients. Dr. Nazha said that this new model has a better predictability index for OS and leukemia-free survival than the IPSS.

Multicenter Microbiota Analysis Indicates that Pre-HCT Microbiota Injury Is Prevalent across Geography and Predicts Poor Overall Survival (811)

The intestinal microbiota composition is associated with important outcomes after allogeneic (allo) HCT including OS, organ toxicity, relapse, graft-versus-host disease (GvHD), and infection. Most studies have looked at the microbiota after transplantation. Jonathan U. Peled, MD, PhD, Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, described this study looking at the intestinal microbiota composition in 1922 stool samples from patients both before and after allo-HCT in three geographic regions.

Dr. Peled said it was striking that no matter where in the world these patients lived, their intestinal microbiota composition and diversity were comparable at baseline. Higher diversity pre-HCT microbiota is associated with better OS than low diversity (HR 0.69; P=.002), as well as with peri-neutrophil engraftment. After transplant, a decrease in diversity and domination of single species are correlated with poorer outcomes.

Approaches that could manipulate microbiota-host interactions to prevent damage include antibiotics, prebiotics, probiotics, and postbiotics.

 

Lynne Lederman, PhD

By Lynne Lederman, PhD

As the 2018 American Society of Hematology (ASH) Annual Meeting continues, we focus on two studies that have the potential to be practice-changing for the treatment of older patients with AML and younger patients with favorable-prognosis diffuse large B-cell lymphoma (DLBCL), the development of a personalized risk stratification model for patients with myelodysplastic syndromes (MDS), and the finding that pre-hematopoietic cell transplant (HCT) microbiota injury is associated with poorer overall survival (OS).

Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies (559)

Results from the Beat AML umbrella study demonstrated that it was feasible to implement a rapid treatment assignment within 7 days or less for 95.8% of elderly patients with AML, reported Amy Burd, PhD, Leukemia and Lymphoma Society.

This precision medicine trial tested the hypothesis that outcomes for patients could be improved by matching them to the increasing number of available targeted therapies. The primary objectives were to determine (1) the feasibility of completing molecular, immunophenotypic, and/or biochemical studies in ≤7 calendar days, (2) the feasibility of assigning patients to sub-studies in the master protocol based on the test results, and (3) the clinical efficacy of novel treatment strategies in each of the sub-studies.

The trial enrolled patients age ≥60 years with previously untreated AML. Treatment was assigned based on the best curative option using molecular profiling results. Median age was 72 years, and 37.9% of patients were age ≥75 years.

So far 365 patients have been enrolled, of whom 285 were assigned treatment; 146 patients received the assigned treatment. Most of the patients who were not treated received other therapies, including standard of care, alternative treatment prior to assignment, or enrollment in an alternative trial after assignment; 7 died during the 7-day period, and 23 opted to enter palliative care.

The trial began with 3 sub-studies, which has since increased to 11 sub-studies, providing more options. Promising efficacy has been seen in several treatment arms, and early death and disease progression prior to treatment assignment is uncommon outside of MLL rearranged AML which progresses rapidly and requires early treatment initiation. Two sub-study updates are being presented at the meeting (abstracts 4053 and 287).

Excellent Outcome of Young Patients (18-60 years) with Favourable-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 4 Cycles CHOP Plus 6 Applications of Rituximab: Results of the 592 Patients of the Flyer Trial of the Dshnhl/GLA (781)

Results of the FLYER trial showed that reducing cycles of CHOP-like chemotherapy from the standard 6 cycles of rituximab (R)-CHOP to 4 cycles of CHOP plus 6 doses of R maintained efficacy and reduced toxicity for younger patients with good prognosis DLBCL.

Viola Poeschel, MD, Department of Hematology, Oncology and Rheumatology, Saarland University Medical School, Homburg/Saar, Germany, presented the results. FLYER enrolled previously untreated patients age 18 to 60 years with stage I/II aggressive B-cell lymphoma, with age-adjusted International Prognostic Index of zero and no bulky disease. Patients were randomly assigned to treatment with 6 cycles or R-CHOP or 4 cycles R-CHOP plus 2 additional cycles of R in 21-day cycles.

The primary endpoint was progression-free survival (PFS). The 36 month PFS was 94% (95% CI 91%-97%) for the 6 x R-CHOP-21 group (n=295), and 96% (95% CI 94%-99%) for the 4 x R-CHOP-21 + 2 x R group (n=293) at a median follow-up of 66 months.

Likewise, the 36-month overall survival (OS) was similar between the treatment groups: 98% (95% CI 96%-99%) in the standard therapy group and 99% (95% CI 98%-100%) in the reduced chemotherapy group at a median follow-up of 67 months.

Fewer hematologic adverse events (AE) were reported in the reduced chemotherapy group, as well as an overall reduction of non-hematologic AEs by approximately one third.

A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes (793)

Current treatment guidelines for MDS are based on risk stratification for progression to AML, and although HCT is potentially curative in high-risk disease, associated toxicities make it inappropriate for low-risk disease. Aziz Nazha, MD, Cleveland Clinic, Cleveland, OH, described the development of a prediction model that uses a machine learning approach to provide a personalized, patient-specific estimate of risk.

Dr. Nazha’s group show that when looking at survival of patients with MDS by Revised International Prognostic Scoring System (IPSS-R) for MDS risk category, outcomes are heterogeneous.

The model was developed using clinical and mutational data from patients with MDS in a combined cohort from the Cleveland Clinic and Munich Leukemia Laboratory (training cohort, n=1471) and validated in a separate cohort (validation cohort, n=831) from the Moffitt Cancer Center. Forty gene mutations commonly occurring in myeloid malignancies were sequenced. Patients undergoing HCT were censored at the time of transplant. An algorithm was used to build the model that randomly selected clinical and molecular variables to determine survival. Variables were ranked from the most to the least important for OS.

A clinic-friendly web application tool has been built from the final model, allowing input of important risk factors to calculate predicted OS for individual patients. Dr. Nazha said that this new model has a better predictability index for OS and leukemia-free survival than the IPSS.

Multicenter Microbiota Analysis Indicates that Pre-HCT Microbiota Injury Is Prevalent across Geography and Predicts Poor Overall Survival (811)

The intestinal microbiota composition is associated with important outcomes after allogeneic (allo) HCT including OS, organ toxicity, relapse, graft-versus-host disease (GvHD), and infection. Most studies have looked at the microbiota after transplantation. Jonathan U. Peled, MD, PhD, Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, described this study looking at the intestinal microbiota composition in 1922 stool samples from patients both before and after allo-HCT in three geographic regions.

Dr. Peled said it was striking that no matter where in the world these patients lived, their intestinal microbiota composition and diversity were comparable at baseline. Higher diversity pre-HCT microbiota is associated with better OS than low diversity (HR 0.69; P=.002), as well as with peri-neutrophil engraftment. After transplant, a decrease in diversity and domination of single species are correlated with poorer outcomes.

Approaches that could manipulate microbiota-host interactions to prevent damage include antibiotics, prebiotics, probiotics, and postbiotics.

 

January 06, 2017 - 11:01 pm Posted in ASH Conference Coverage Posted in Lymphoma (includes NHL, HL, CNS Lymphoma) comments0 Comments

Introduction

In an effort to provide you with timely market feedback from the 58th ASH Annual Meeting held in December 2016, OBR and MDoutlook® are pleased to share results from MDoutlook’s OncoPolls™ conducted last month immediately after the meeting. This report explores the choice between Rituxan® and Gazyva® in the front line setting for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and the use of Rituxan and Revlimid® in the maintenance setting for mantle cell and CLL, respectively.

OncoPoll™ Methodology

  • Primary research phase involved a survey to verified and validated US hematological and medical oncologists with an identified clinical interest in B-cell lymphomas utilizing targeting parameters within the proprietary MDoutlook global cancer treater panel
  • Timing: December 2016. Launched 9 days after close of 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA, December 3-6, 2016
  • Fielding to proprietary panel of cancer treaters, targeted by clinical interest
  • Data capture via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASH website were provided within the survey
  • Reponses at data collection: 100

Institutional Setting by Attendance of Respondents

oncopoll_nhl_attendance

Use of anti-CD20 mAbs in the Front Line for Different B-cell Lymphomas

Awareness of Abstracts #6 & #470

oncopoll_nhl_awareness

 General Clinical Importance of Different anti-CD20 mAbs in FL & DLBCL

oncopoll_nhl_importance

Expected Impact on anti-CD20 Usage in FL & DLBCL

 oncopoll_nhl_impact

Key Conclusions

  • On a 0 – 5 scale of 0 = no awareness to 5 = very aware, clinicians have only an average / slightly below average awareness of these presentations
    • A general higher level of awareness is seen by those who attended ASH (nearly a full rating point higher for each abstract)
    • The average level awareness about the FL abstract is somewhat lacking considering it was presented in the Plenary Session
  • Clinical impact of these presentations, rated on a 1 – 5 scale of 1 = not at all important to 5 = very important, is seen as being very clinically meaningful
    • US oncologists assign a high importance (>4) to the FL presentation (Abstract #6), regardless of meeting attendance
    • Abstract #470 (concerning DLBCL) is seen as somewhat less important, especially by those who did not attend the meeting
  • Expected impact on anti-CD20 mAb usage in their practice was also measured. A 14-22% absolute growth in usage of Gazyva is predicted in the near future, all at the expense of Rituxan usage. No real changes noted in patients not treated with anti-CD20 antibodies or with other anti-CD20 antibodies (not shown). With greater impact seen with non-attendees, this shows the importance of the information itself, compared to the need to be present at the meeting for changing practices.

Use of Maintenance Strategies for Mantle Cell Lymphoma and CLL

Awareness of Abstracts #145, #229 & #230

oncopoll_nhl_maintenance-mcl-cll

General Clinical Importance of Maintenance Strategies for Mantle Cell Lymphoma and CLL

oncopoll_nhl_importance-mcl-cll

Expected Impact on Maintenance Usage in Mantle Cell Lymphoma and CLL

oncopoll_nhl_impact-mcl-cll

Key Conclusions

  • On the same 0 – 5 scale, attendees of the ASH meeting have an average level awareness about these maintenance presentations, while awareness by non-attendees is low
    • No meaningful differences in awareness among these three abstracts
  • Upon providing these abstracts for review, US oncologists recognize the clinical importance of this information and plan on incorporating these maintenance strategies into their clinical practices immediately
    • Meeting attendance does not really impact these findings. In fact, non-attendees may be more likely to use these approaches in their practices

Conclusions: Immediate Impact of 2016 ASH Presentations on Clinical Practice for B-cell Lymphomas

  • All of these studies highlight the importance of the ASH Annual Meeting to the entire hematologic oncology community – awareness of these presentations are high and can occur quite quickly even for those who did not attend the meeting. Alternative methods to disseminate new clinical information are very important to improving clinical practices and patient outcomes
  • The information in these presentations will be integrated into clinical practice in relatively short order, especially since most of these agents are already widely available and in use

For a more detailed analysis report, please click here to download the full report.

Submitted by Dr Robert Stephan, VP, Research and Physician Society, and Dr Jan Heybroek, President MDoutlook.

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