July 2015 Edition Vol.9, Issue 7

European Hematology Association: Remains of the Day

European Hematology Association: Remains of the Day

By Neil Canavan

Each year, the European Hematology Association (EHA) annual meeting takes place on the heels of ASCO.  Although the lion’s share of data presented at the American Society of Clinical Oncology (ASCO) 2015 annual meeting involved the treatment of solid tumors, hematologic malignancies got their share of attention this year.

But why would anyone put themselves through the rigors of two nearly back-to-back cancer meetings?  Anton Hagenbeek, MD, PhD, Department of Hematology, University of Amsterdam, The Netherlands, the moderator for the EHA press conference, may have summed it up best: “Treatment of solid tumors is relatively straightforward, but blood cancers are far more interesting.”

That said, if you didn’t make the trip to Vienna, here are a few of the many interesting clinical trials presented there: one presentation featured a new player within the modality of cancer immunotherapy; another showed a new antibody-drug conjugate; another presentation involved a novel agent that triggers cancer cell death through apoptosis; and the last one we offer, features an old drug in search of a new indication – and this, just as the patent for this compound is about to run out. 

Elotuzumab in the treatment of Multiple Myeloma

Elotuzumab is a monoclonal antibody targeted to SLAMF7 (Signaling Lymphocyte Activation Molecule, Family 7), a target present on natural killer (NK) cells of the immune system, as well the cancerous cells of multiple myeloma.

“We believe the drug works by a dual mechanism,” said Meletios Dimopoulos, MD, who presented the results for the ELOQUENT-2 trial, featuring elotuzumab (ELO). “When the drug binds to SLAMF7 on NK cells it directly activates them. When it binds to SLAMF7 on myeloma cells, that flags them for NK cell recognition and destruction.”

ELOQUENT-2 is a phase 3 investigation of ELO added to the standard-of-care (SOC) combination of lenalidomide/dexamethasone, as compared to the SOC alone in a cohort of relapsed/refractory patients with multiple myeloma.

Multiple myeloma is the second most common hematologic malignancy with a median age of onset of 65; due to the aging of the general population, the incidence rate for this disease is rapidly increasing. “So we need not only more active regimens, but regimens that will be well tolerated by patients who are advanced in age,” said Dr. Dimopoulos.

Despite significant progress in the overall survival of the disease, the majority of multiple myeloma patients continue to relapse, and eventually become resistant to any kind of therapy. It is hoped that the approach taken in ELOQUENT-2—ELO plus SOC—
will overwhelm resistance mechanisms.  

Results for the ELOQUENT-2 trial, thus far, support that hope. At a median follow-up time of 24 months, results for the ELOQUENT-2 investigation (N=646) show a 30% reduction in the risk of disease progression and/or death.

The rate of progression-free survival for the triplet was 41% vs. 27% for SOC; and the overall response rate was 79% with the addition of ELO vs. 66% for SOC (p=0.0004). 

Results were consistent across patient groups when stratified by age, performance status, and cytogenetic profile.

Regarding safety, with the exception of moderate infusion reactions, there were no appreciable differences in the toxicity profile for the triplet combination with ELO, as compared with SOC.

Perhaps as a hangover effect from ASCO, where prices for novel agents came under open attack – in the plenary session – Dr. Dimopoulos was asked about the potential cost of this likely-to-be-approved agent (breakthrough status for ELO was granted by the FDA in 2014): “As we know, financial toxicity is one of the side effects in the treatment of most hematologic malignancies,” he responded, “and of course we don’t know where pricing will be set. But if I had to guess from my prior experience  it will be very expensive.”

Editors note: Just days after the EHA meeting ended, both ASCO, and Memorial Sloan Kettering Cancer Center (MSKCC) announced their respective launches of programs aimed at evaluating drug costs as compared to their benefits. ASCO rolled out their initial version of, “a conceptual framework for assessing the value of new cancer treatment options…” and MSKCC trumpeted their new “DrugAbacus, an interactive exploration of drug pricing.”

Inotuzumab Ozogamicin

Inotuzumab Ozogamicin (INO) is a molecular Trojan horse: it is an antibody targeting the CD22 receptor, tethered to a payload of a type of calicheamicin, a class of potent antitumor antibiotics. When INO binds to its target the molecule is internalized, the calicheamicin component is released under acid hydrolysis, binds to DNA in the target cell, and thereby kills it.

CD22 is expressed on the surface of roughly 90% of all B-cells in acute lymphocytic leukemia (ALL).  

The unmet need in managing this disease is clear. “ALL remains very difficult to treat, with a paltry 5-year overall survival of less than 10%,’ said Daniel DeAngelo, MD, PhD, Dana Farber Cancer Institute, Boston, who presented the data for INO. 

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