ASH: Amgen's Blincyto looks to establish new leukemia standard after 9-year trial

A clinical trial that started before the first FDA approval for Blincyto might support a new use for the Amgen therapy in acute lymphoblastic leukemia (ALL).

Blincyto helped patients with newly diagnosed B-lineage ALL who had a good prognosis after an initial round of chemotherapy live longer, according to data presented at the 2022 American Society of Hematology (ASH) annual meeting.

In ALL patients who achieved no minimal residual disease (MRD) after induction chemo, adding Blincyto to chemotherapy during the consolidation phase significantly reduced the risk of death by 58% over chemo alone in a phase 3 trial coded E1910. After 3.5 years of follow-up, 83% patients in the Blincyto combo arm were still alive. That compared with 65% in the chemo-only group.

The study was designed to enable an FDA application, lead investigator Mark Litzow, M.D., from the Mayo Clinic, told Fierce Pharma. The research alliance ECOG-ACRIN led the trial with funding from the National Cancer Center, and Amgen also contributed.

In a statement to Fierce Pharma, Amgen said it plans to discuss with global regulatory authorities “the suitability of data” for a potential Blincyto indication as a consolidation therapy in MRD-negative ALL.

Thanks to an FDA expanded approval in 2018, Blincyto is currently allowed to treat MRD-positive patients. That approval defines MRD-positive as having at least 0.1% leukemic cells in the bone marrow. In the ECOG trial, however, only patients with less than 0.01% MRD were considered MRD-negative.

Typically, about 80% to 90% of ALL patients can achieve a conventional complete remission after induction therapy, and about two-thirds of those patients can reach MRD-negative status, Litzow said. MRD-negative patients have a better prognosis than their MRD-positive counterparts.

The trial started in December 2013, one year before Blincyto got its initial FDA nod to treat patients with an uncommon form of the disease called Philadelphia chromosome-negative B-cell ALL.

In the E1910 study, 224 MRD-negative patients were randomized 50/50 to receive either standard chemo or chemo plus Blincyto during the consolidation phase, which included continuous intravenous infusion for four weeks during each of the four cycles of treatment.

The results mean that adding Blincyto to consolidation chemo “represents a new standard of care” for patients with newly diagnosed B-cell ALL with no measurable residual disease after induction chemo, Litzow said in a statement.

Blincyto is a relatively small part of Amgen’s business, generating third-quarter sales of $142 million, a 14% increase from the same period last year.

Blincyto also competes with Pfizer’s antibody-drug conjugate Besponsa in relapsed or refractory B-cell precursor ALL. At ASH 2022, a group of researchers in Germany reported positive results for a single-arm trial of Besponsa in newly diagnosed ALL.

Unlike Blincyto’s E1910 trial, the German team tested Besponsa as part of an induction therapy followed by conventional chemo. All 43 patients achieved a complete remission after induction, and 74% of patients became MRD-negative after the last induction therapy. Based on the high remission rate, the German team suggested the results “could be a rationale” for integrating Besponsa to induction therapy in future treatment and recommended a randomized clinical trial to validate the idea.

“What you’re going to see is … that we’re likely going to be moving these immunotherapies up closer to the time of diagnosis,” Litzow said, noting that the current E1910 trial was designed over 10 years ago.

Meanwhile, Amgen is running a phase 3 trial comparing Blincyto alternating with low-intensity chemo versus conventional chemo for older adults with newly diagnosed Ph-negative B-cell precursor ALL.

Gilead Sciences’ CAR-T therapy Tecartus and Novartis’ Kymriah are also allowed in relapsed or refractory B-cell precursor ALL.

“I think it may well come that we will use little or no chemotherapy in these patients,” Litzow said. He noted that researchers are also evaluating the combination of Besponsa and Blincyto and that some doctors are already treating front-line MRD-positive patients with CAR-T therapy.

While CAR-T therapies are currently only approved for relapsed patients, Litzow said he believes they will likely move into early treatment.