The OBR Blog

One of biggest challenges in attending an annual ASCO meeting is time management. With over 2,000 abstracts submitted this year and a wide variety of new drugs and therapeutic targets, ASCO 2019 will be no different.

During a webinar last week sponsored by E-Squared Communications (a Conisus company), OBR and three renowned cancer experts helped identify some of the “high impact studies” that are sure to gain a lot of attention at this year’s ASCO Annual Meeting. For those of you who missed this increasingly popular annual webinar, the experts not only covered the important data but also provided some suggestions on where to go if you happen to play hooky for a day at ASCO. Don Sharpe, President and Founder of OBR, moderated the session, and the primary areas of focus included cervical, prostate, pancreatic, breast, lung, and advanced gastric/gastroesophageal junction cancers as well as multiple myeloma and hepatocellular carcinoma (HCC).

Pending its final outcome, the first trial highlighted in the webinar could well be a practice-changing study. This phase 3 Intergroup trial (E3A06) in patients with asymptomatic intermediate- or high-risk smoldering multiple myeloma is the largest randomized trial in this setting to date. The 182 patients who participated in this study were randomized to either receive lenalidomide alone or observation, with progression-free survival (PFS) being the primary endpoint. At a median of 28 months of follow-up, the 3-year PFS rate in the lenalidomide arm seems to be numerically trending in the right direction (91% vs. 66%). This data will be highlighted in an oral abstract (8001) session on Sunday, June 2nd.

Following an interesting review of a phase 2 study highlighting the use of LN-145 tumor infiltrating lymphocytes in patients with cervical cancer, the next phase 3 study highlighted by the experts was a late-breaking abstract. This Australian and New Zealand Urogenital (ANZUP) Cooperative Group trial (ENZAMET) evaluated enzalutamide as first-line androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer. The abstract LBA2 will be presented at the plenary session on Sunday, June 2nd and is sure to draw comparisons to the earlier LATITUDE study of abiraterone in this setting.

Pancreatic cancer seems to be climbing into the spotlight as well this year, as the OBR experts identified the Adjuvant Treatment in Pancreatic Cancer Study (APACT) as an important one to watch. This study evaluated nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with surgically resected pancreatic cancer. With 866 patients enrolled, this large clinical trial had a primary endpoint of disease-free survival; however, the authors noted that the overall survival (OS) results seen in this study may better support the rationale of using this combination in the adjuvant setting, especially for patients who are ineligible for FOLFIRINOX.

The PARP inhibitor olaparib was also discussed in the webinar as a potentially new therapeutic option for patients with pancreatic cancer. The phase 3 POLO trial of olaparib versus placebo as maintenance therapy in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease had not progressed following first-line platinum-based chemotherapy will be highlighted during the plenary session on Sunday, June 2nd (LBA4). This study is the first positive phase 3 trial of any PARP inhibitor in germline BRCA-mutated metastatic pancreatic cancer.

Pembrolizumab was highlighted as well in two studies looking at gastric cancer and GEJ adenocarcinoma (KEYNOTE-062) and advanced HCC (KEYNOTE-240). In KEYNOTE-062, pembrolizumab met its primary endpoint by demonstrating OS noninferiority compared to chemotherapy in the intent-to-treat population. In KEYNOTE-240, pembrolizumab showed positive numerical trends but did not meet statistical significance for its co-primary endpoints of OS and PFS; however, it did show an improved response rate versus placebo (ORR 16.9% vs. 2.2%), and it will be interesting to see what impact this might have going forward.

Another important KEYNOTE study is KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC. KEYNOTE-001 is also a late-breaking abstract looking at 5-year long-term OS for patients with advanced non-small cell lung cancer treated with pembrolizumab.

There are certainly other important abstracts at this year’s ASCO Annual Meeting, but at the very least, this review should help narrow down your choices.

By Adrian Barfield, President, Medallion Healthcare

May 15, 2019 - 10:05 pm Posted in ASCO Conference Coverage Posted in Breast Posted in Multiple Myeloma Posted in Pediatric (includes Adolescents and Young Adults) comments0 Comments

In conjunction with the release of the abstracts for the upcoming 2019 ASCO Annual Meeting, a virtual press cast previewed five noteworthy studies that showcase the range of research that will be presented at the meeting.

Topics included the effect of a low-fat diet on breast cancer mortality, identification of a greater than expected number of targetable molecular alterationsin a pediatric MATCH trial, response of rare pediatric tumors with certain gene fusions to the targeted agent entrectinib, optimization of chemotherapy for frail and/or elderly patients with advanced esophageal cancer, and reduction of progression of smoldering to active multiple myeloma by lenalidomide.

Here are summaries of the key findings.

Low-Fat Diet Associated with Reduced Breast Cancer Mortality (Abstract 520)

Observational studies of the effect of dietary fat on breast cancer have produced equivocal results. To address this, the Women’s Health Initiative (WHI) Dietary Modification (DM) trial, a randomized, controlled study looked at the influence of diet breast cancer incidence and mortality.

The WHI-DM trial (NCT00000611) enrolled 48,835 post-menopausal women age 50 to 79 years who were randomly assigned to dietary intervention (n=19,541) or usual diet (comparison group, n=29,294) from 1993 to 1998. Dietary intervention, which continued for 8.5 years, included reducing fat intake to 20% of calories and increasing intake of vegetables, fruit, and grains, similar to the DASH (dietary approaches to prevent hypertension) diet.

Trial endpoints included deaths from and after breast cancer. Cumulative follow-up data have been collected for a median of 19.6 years. Baseline fat intake was at least 32% of calories. Most women in the diet group increased daily intake of vegetables, fruit, and grains and reduced daily fat consumption to 25% of calories; most did not reach the 20% goal.

In the diet group versus the comparison group, there was a significantly lower risk of death from breast cancer (HR, 0.85; 95% CI, 0.74, 0.96; P=.01) and from any cause after a diagnosis of breast cancer (HR, 0.79; 95% CI, 0.64, 0.96; P=.025).

The authors call this the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer, although this analysis was not pre-specified in the original trial design, dietary components were assessed by participant recall, and there was no way to measure adherence to the diet.

At the meeting, the effect of the same dietary modification in a subgroup of women with poor metabolic function, defined as obesity, diabetes, elevated cholesterol, or hypertension, will also be presented (Abstract 1539).

More Actionable Targets than Expected Found in Pediatric MATCH Trial (Abstract 10011)

The NCI-COG (Children’s Oncology Group) Pediatric MATCH (Molecular Analysis for Therapy Choice) trial was designed to address whether a precision oncology approach, i.e., treating tumors with agents selected to target specific genetic alterations, would be useful in the pediatric cancer setting.

NCI-COG Pediatric MATCH will enroll at least 1000 children with tumors that have not responded to standard treatment. The initial step is to screen tumors for potential targets, followed by treatment with therapy matched to alterations found in the tumors independent of tumor type. Treatment is in individual phase 2 clinical trials, of which there are currently 10, one for each current single-agent targeted therapy being tested.

There were 422 patients enrolled, from 93 of the 124 COG sites that had the study open, between July 24, 2017 and the data cutoff for this analysis at the end of last year. Tumor samples were received from 92% of enrolled patients and accounted for over 60 different tumor types including central nervous system (CNS) and non-CNS tumors. Turnaround time was 15 days from tumor receipt to treatment assignment.

Study researchers projected a match rate of 10% based on adult data. So far, 24% of screened patients with cancer that did not respond to treatment were eligible for treatment with a targeted agent. Of these, 39 patients (10%) have enrolled in a treatment trial. The trial is ongoing and is expected to add at least four additional single targeted agents. Combination therapies are being considered for future trials.

Rare Pediatric Tumors with Gene Fusions Respond to Entrectinib in Early Trial (Abstract 10009)

Fusions and alterations in intracellular signaling pathways such as TRKA/B/C, ROS1, and ALK genes act as drivers in some tumors by “locking” the pathways in the “on” position. Entrectinib is an oral inhibitor of these pathways and has the additional advantage of being able to cross the blood-brain barrier to enter the CNS.

Pediatric tumors with mutations in TRKA/B/C, ROS1, and ALK genes are rare, and are being identified more frequently as next-generation sequencing is becoming more common. STARTRK-NG (RXDX-101-03) is phase1/1b clinical trial investigating entrectinib in children with recurrent or refractory solid tumors with these gene alterations. Most had undergone prior surgery and radiation.

Of 29 patients enrolled, 16 were in the phase 1 dose-finding part; an additional 13 patients have been enrolled in the ongoing basket phase 1b part at a dose level of 550 mg/m2(initial recommended dose, n=7) or 400 mg/m2for those unable to swallow intact capsules. Diagnoses included primary CNS tumors (n=6), neuroblastoma (n=3), and extracranial solid tumors (n=4). Median patient age is 7 years.

Responses have been seen in all patients whose tumor had a target gene alteration and no responses were seen in patients whose tumors lacked aberrations in target kinases. Therefore, the trial will continue only for patients with target fusions. Presenter Giles W. Robinson, MD, St. Jude Children’s Research Hospital, Memphis, Tennessee, said, “It gives me great pleasure as pediatric brain tumor doctor to show response in CNS tumors” that would otherwise probably have been fatal.

Dose-limiting toxicities included elevated creatinine, dysgeusia, fatigue, and pulmonary edema. Weight gain, problematic for some patients, also occurred as an on-target drug effect. Side effects have resulted in dose reduction to 400 mg/m2.

Dose-Modified Chemotherapy for Frail and/or Elderly Patients with Advanced Gastroesophageal Cancer (Abstract 4006)

Although the average age of patients at the time of diagnosis of advanced, inoperable gastroesophageal cancer is 75 years, and many patients are frail, standard of care chemotherapy has been developed in trials in patients with an average age of 65 years who are generally not frail. This study was motivated by the finding that a survey of oncologists in the UK used reduced dose chemotherapy regimens that were not evidence-based to treat frail and/or elderly patients with gastroesophageal cancer.

A prior phase 2 trial indicated that a 2-drug regimen was preferable to 3-drug or single agent regimens in this setting. The GO2 phase 3 trial was designed to optimize doses of 2-drug chemotherapy regimens and assess benefits and risks.

Patients (n=514) with a median age of about 76 years who were fit for chemotherapy but not for full-dose, 3-drug regimens were enrolled. There were 2 randomization schemes based on whether the patient was considered either certain or likely to benefit from chemotherapy and basic supportive care (BSC) was not appropriate (certain randomization), or would derive uncertain benefit from chemotherapy with BSC possibly appropriate (uncertain randomization). Presenter Peter S Hall, PhD, University of Edinburgh, Edinburgh, UK, discussed the certain randomization option, where patients were randomly assigned to one of 3 dose levels of combinations of oxaliplatin plus capecitabine.

In addition to assessing progression-free survival (PFS), and a non-inferiority boundary agreed upon by a patient focus group and clinicians, the study also determined which dose level resulted in the best “overall treatment utility (OTU),” a novel concept developed in phase 2, which included cancer control, severity of side effects, patient quality of life (QoL), and oncologist’s assessment of benefit.

The lower doses of chemotherapy were non-inferior to the highest dose for median PFS (4.9 months for the highest dose, 4.1 months for the intermediate dose, and 4.3 months for the lowest dose), as well as for median overall survival (7.5 months, 6.7 months, and 7.6 months, respectively). The lowest dose was associated with the best OTU scores, as a result of fewer side effects and better quality of life (QoL).

Lenalidomide Reduces the Risk of Progression from Smoldering to Active Multiple Myeloma (Abstract 8001)

Smoldering or asymptomatic multiple myeloma (SMM) is a precursor to symptomatic MM. The goal of the phase 2/3 E3A06 trial was to determine if early intervention in intermediate or high risk SMM using low-intensity, single-agent lenalidomide could prevent progression to MM. The primary endpoint was time to develop MM.

In phase 2, the safety of 25 mg daily of lenalidomide for 3 out of every 4 weeks was determined. Phase 3 randomly assigned patients to the same dose of lenalidomide (n=90) or to observation (n=92). Prophylactic aspirin was administered with the lenalidomide.

Time to develop MM was delayed with the use of lenalidomide (2-year PFS probability 0.93; 95% CI, 0.88-0.99) compared with observation (2-year PFD probability 0.76; 95% CI 0.66-0.87). Treatment-related grade 3 and 4 hematologic and non-hematologic adverse events were observed with lenalidomide; 51% of patients in the phase 3 portion discontinued due to toxicity, although there was no difference in QoL reported between the 2 groups.

Three-year PFS was 91% in the lenalidomide group, compared with 66% in the observation group (HR 0.28, P=.0005). Follow-up is too short to determine the effect of treatment on overall survival. The investigators will follow patients who discontinued to see if limited doses of lenalidomide can delay progression of SMM to MM. This study shows early intervention, at least in patients with higher risk SMM, can prevent MM and its associated end organ damage.

By Lynne Lederman, PhD

PS – Don’t forget to sign up for our ASCO ’19 Preview webinar featuring Lee Schwartzberg, MD, Zev Wainberg, MD, and Rich Leff, MD. Register here.

As the ASH Annual Meeting concludes, the late-breaking abstracts are always of great interest. We take a brief look at one non-malignant hematology presentation that has implications for oncology, as well as three malignant hematology presentations on advances in targeted therapies for CLL and multiple myeloma.

Rivaroxaban Thromboprophylaxis in High-Risk Ambulatory Cancer Patients Receiving Systemic Therapy: Results of a Randomized Clinical Trial (CASSINI) (LBA-1)—short summary of this one

Patients with cancer have a higher risk for venous thromboembolism (VTE), which can lead to death, morbidity, hospitalization, and delay in cancer treatment.

Alok A. Khorana, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, reported results of the CASSINI trial (NCT02555878), a double-blind, randomized, placebo-controlled, parallel-group, multicenter study in adult ambulatory patients with various cancers initiating a new systemic regimen and at increased risk for VTE, defined as Khorana score ≥ 2 for a risk-adapted approach to prophylaxis.

Patients were randomly assigned to rivaroxaban, a direct oral anticoagulant (n=420), or to placebo (n=421) for 6 months. An important aspect of the trial was the use of ultrasonography of the lower extremity at baseline to identify pre-existing clots, which occurred in 4.5% of screened patients who were therefore not enrolled.

There was no significant difference between groups in the primary efficacy outcome of cumulative thromboembolic events; 38.7% of events occurred in patients who had discontinued treatment. For patients who remained on treatment, rivaroxaban significantly reduced events (2.62%) versus placebo (6.41%; P=.007), and significantly reduced a composite of the primary endpoint and all-cause mortality (P=.003).

There were no significant differences in safety outcomes between the groups for bleeding. A risk-benefit analysis showed that the number needed to treat (NNT) was 26 for patients who remained on treatment. The number needed to harm (NNH) was 101 for major bleeding and 135 for clinically relevant non-major bleeding for patients on treatment.

Dr. Khorana concluded that baseline screening for VTE could be considered for patients starting systemic cancer therapy. The findings of this study, along with a similar study that has just concluded, should inform future recommendations for thromboprophylaxis for higher-risk ambulatory patients with cancer.

Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA) (LBA-2)

Thierry Facon, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France, presented the pre-specified interim analysis of the MAIA study, a phase 3 trial evaluating daratumumab plus lenalidomide and low dose dexamethasone (D-Rd) versus Rd in patients with transplant-ineligible, newly diagnosed multiple myeloma. Daratumumab is a human, CD38-targeted, IgG1κ monoclonal antibody.

Patients were randomly assigned to D-Rd (n=368) or Rd (369); treatment continued until disease progression. Median age was 73 years, and notably, 44% of patients were age ≥75 years. The primary endpoint was progression-free survival (PFS).

At a median follow-up of 28 months there was a 44% reduction in risk of progression or death in the D-Rd group (71% at 30 months vs 56% for placebo; HR 0.56; 95% CI 0.43-0.73; P<.0001). Median PFS in the Rd group was 31.9 months and not reached in the D-Rd group. This benefit was seen across most sub-groups analyzed.

The overall response rate was 93% for D-Rd versus 81% for Rd (P<.0001); complete response rates and at least very good partial response rates were higher for D-Rd than for Rd. The minimal residual disease (MRD)-negative rate was significantly higher for D-Rd (24%) than for Rd (7%; P<.0001). Patients who were MRD negative had longer PFS. There is no difference between groups in overall survival (OS) at this follow-up time.

The safety profile was consistent with that seen for these combinations in other studies. Because of the inclusion of lenalidomide, the incidence of secondary primary malignancies (SPM) was determined; it was 3% for D-Rd and 4% for Rd; hematologic SPM occurred in 0.5% of each arm.

Dr. Facon concluded that the results of this study support D-Rd as a new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma.

A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912) (LBA-4)

The E1912 (NCT02048813) trial showed that ibrutinib plus rituximab (IR) improves PFS and OS compared with fludarabine, cyclophosphamide, and rituximab (FCR) in younger patients with previously untreated CLL. FCR has been the most active chemo-immunotherapy to date for CLL and has not been compared with ibrutinib as an initial treatment for younger patient with CLL.

Patients age ≤70 years (median age 58 years) with CLL were randomly assigned 2:1 to IR (n=354) or to 6 cycles of FCR (n=175). Patients in the IR group received 1 cycle ibrutinib, 6 cycles IR, then ibrutinib until disease progression.

At a median follow-up of about 3 years, PFS was significantly longer in the IR group (HR 0.35; 95% CI 0.22-0.5; P≤.00001), as was OS (HR 0.17; 95% CI .05-0.54; P≤.0003). Neutropenia, anemia, thrombocytopenia, and neutropenic fever occurred significantly less often with IR than FCR; atrial fibrillation and hypertension occurred significantly more often with IR than FCR. There were no significant difference in infection, bleeding, or diarrhea.

Presenter Tait D. Shanafelt, MD, Stanford University, Stanford, CA, concluded that these results establish IR as the most effective first-line therapy in patients age ≤70 years with CLL.

Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia (LBA-7)

Venetoclax, a selective BCL2 inhibitor induces deep and durable responses in CLL. However, most patients treated with venetoclax will eventually experience disease progression, and the mechanisms of resistance to venetoclax in patients are largely unknown.

This study looked at 67 patients with relapsed CLL; 21 had CLL-type progressions; of these, 15 had samples suitable for genomic analysis. A new mutation that was not present in pre-treatment samples, BCL2 Gly101Val, was detected in four patients using targeted amplicon sequencing. This is the first acquired BCL2 mutation described in patients with CLL treated with venetoclax. BCL2 Gly101Val occurs in the BH3-binding groove and has not been detected in other B-cell malignancies. BCL2 Gly101Val reduces the binding of venetoclax to BCL2 as much as 180-fold.

Piers Blombery, MBBS, University of Melbourne, Melbourne, Australia, said that they have detected BCL2 Gly101Val in patient samples months to years before relapse, and the mutation has subsequently been detected in three additional patients in the original group of 15 studied.

Cell lines overexpressing BCL2 Gly101Val are resistant to venetoclax and the mutation confers a growth advantage over wild-type cells in the presence of the drug.

Dr. Blombery pointed out that alternative resistance mechanisms can co-exist with BCL2 Gly101Val. These study results could provide a rationale for a limited time course for venetoclax.

This year’s ASH Annual Meeting will be chock-full of interesting, informative, and clinically useful presentations, according to a whirlwind tour of highlights presented at a pre-meeting Webinar by ASH President Charles Abrams, MD, and Stephanie Lee, MD, ASH Secretary.

Starting with the most immediately clinically applicable studies, Dr. Lee singled out two studies of approved agents in narrow disease states: Abstract 182 and 145.

Abstract 182 provides results of the Phase 3 ALCANZA trial comparing brentuximab versus physician’s choice of therapy (methotrexate or bexarotene) in CD30-expressing cutaneous T-cell lymphoma (CTCL), a relatively rare disease. The study included 128 randomized patients followed for 17.5 months. For the primary endpoint, overall response rate (ORR) at 4 months, brentuximab was significantly superior to physician’s choice of therapy: 56% versus 13%, respectively (P<.0001). Median progression-free survival (PFS) was 16.7 months versus 3.5 months, a highly significant difference favoring brentuximab (P<.0001).

“This study showed that brentuximab has a significant advantage over the other two options used to treat CTCL,” Dr. Lee told listeners.

Abstract 145 presents final results of the Phase 3 LyMa trial that compared rituximab maintenance every 2 months for 3 years versus observation in younger patients with mantle cell lymphoma (MCL) in response after undergoing autologous stem cell transplant (ASCT). The study included 240 patients with a median follow-up of 50 months. Four-year event-free survival (EFS) was 78.9% for rituximab maintenance versus 61.4% for observation (P=.0012). Four -year progression-free survival (PFS) and overall survival (OS) were also improved with rituximab maintenance therapy. Four-year PFS was 8.2.% versus 64.6%, respectively (P=.0005), and 4-year OS was 88.7% versus 81.4%, respectively (P=.0413).

“This study provides good evidence that rituximab improves outcomes after ASCT in younger patients with mantle cell lymphoma. Some hematologists are already doing this, and now there is evidence [to support this practice] from a Phase 3 trial,” Dr. Lee noted.

Abstract 6 showed a 34% reduction in risk of progression or death with obinutuzumab versus rituximab as induction and maintenance therapy in about 1200 patients with previously untreated follicular lymphoma with Stage 3 or 4 or bulky Stage 3 disease, according to primary results of the Phase 3 GALLIUM trial.. Patients were randomized 1:1 to obinutuzumab versus rituximab (both anti CD20 agents) at induction. No difference in complete response or partial response was observed after induction therapy. Patients continued on maintenance therapy for 2 years. More Grades 3 and 5 severe adverse events occurred with obinutuzumab.

“These data show that obinutuzumab is more effective in prolonging time to relapse, but the caveat is greater toxicity,” Dr. Lee commented.

CAR-T THERAPY

Dr. Abrams highlighted two studies using genetically engineered chimeric antigen receptor (CAR) T cells. A late-breaker (Abstract LBA 6) showed that Kte-CD19 CAR T cells induced responses in 76% of 101 patients from 22 institutions with refractory diffuse large B-cell lymphoma in the pivotal Phase 2 ZUMA-1 trial. ORR was 76% (47% complete response [CR] rate and 29% partial response rate [PR]). PFS was 56% at 3 months, which Dr. Abrams called “impressive.”

“The T-cells were engineered within 17 days from apheresis, which is a relatively quick turnaround. This treatment is not for the faint of heart, but it does induce complete remissions in some patients. This novel technology can be extended to many centers in the community, even those with no experience using CAR T,” Dr. Abrams noted.

A second study (Abstract 650) found that anti-CD22 CAR T cells had encouraging results in a small study of 9 “tough to treat” patients (children and young adults) with relapsed/refractory acute lymphoblastic leukemia (ALL). All 9 patients had at least 1 prior transplant, and 2 had undergone 2 prior transplants. Patients had chemotherapy and then were given anti-CD22 CAR T. Interim results at 1 month showed that 4 of the 9 patients had CR with no evidence of minimal residual disease.

“This approach with CAR T is a little different, aimed at a different target of T cells with CD 22 expression. This is encouraging, suggesting that the target of CAR T can be expanded. Someday we may be using a panel of targets,” Dr. Abrams commented.

OTHER HEMATOLOGIC MALIGNANCIES

Patients with high-risk chronic lymphocytic leukemia (CLL) were randomized 2:1 to lenalidomide maintenance versus placebo after front-line chemotherapy in the randomized, controlled, German CLLM1 trial (Abstract 229). Interim analysis of the first 89 patients of a planned enrollment of 200 showed such robust results for lenalidomide, that the trial was stopped early. At a median follow-up of 17.7 months, PFS was not yet reached in the lenalidomide-treated group versus 14.6 months for placebo. Patients treated with lenalidomide were 80% more likely to be converted to node-negative disease compared with placebo. No difference in OS was observed between the two groups with short follow-up.

“These interim findings suggest that lenalidomide maintenance is beneficial in high-risk CLL. We need continued follow-up of these patients,” Dr. Lee commented.

Although the investigational drug pacritinib was found effective in myelofibrosis in a Phase 3 trial (Abstract LBA 5), development of the drug was put on hold by the FDA due to potential cardiovascular excess deaths and hemorrhagic events in the PERSIST-1 trial. The Phase 3 PERSIST-2 study evaluated pacritinib versus best available therapy (including the JAK inhibitor ruloxitinib in 44%) in 311 patients with myelofibrosis and platelet counts <100,000 µ/l. Patients were randomized 1:1 to pacritinib versus best available therapy. Pacritinib was superior, with a 35% reduction in spleen volume, and significantly more improvement in time to symptoms at 24 weeks. Although some gastrointestinal and hematologic toxicities were observed with pacritinib, no difference between the two treatment arms was seen in cardiovascular events and bleeding.

PERSIST-2 is the only randomized trial to date in patients with myelofibrosis and thrombocytopenia and prior JAK2 inhibitor exposure. “This study is intriguing. Pacritinib did improve symptoms and spleen volume, but it remains to be seen what the FDA will do,” Dr. Lee said.

Another late-breaking abstract (LBA 1) was based on the randomized, controlled, Phase 3 StaMINA trial, which compared three different approaches to multiple myeloma in transplant-eligible patients using upfront autologous hematologic cell transplant (auto HCT): auto HCT plus RVD (bortezomib, lenalidomide, dexamethasone); tandem auto HCT plus lenalidomide maintenance (TAM); and auto HCT with lenalidomide maintenance (AM). The study enrolled 758 patients. At 38 months, PFS and OS were similar in all three groups. The probability of PFS was 57%, 56%, and 52% for the three approaches, respectively; the probability of OS was 86%, 82%, and 83%, respectively.

This is the largest randomized U.S. transplant trial in myeloma. “Results of StaMINA suggest that the addition of more chemotherapy or more transplant does not improve outcomes. All of these are reasonable approaches,” Dr. Lee noted.

SESSION ON QUALITY

Turning to a different area, Dr. Lee cited a Special Symposium on Quality of Care in the Era of Health Improvement Technology. Three different speakers will tackle the question of whether the new technology is having an impact on patient care.

“I hope this symposium will dig into the current experience for patients and for researchers,” she said.

“There is something for everyone at the upcoming ASH meeting,” she noted.

 

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