The massive investment of time, energy and money into the oncologic drug development space over the past decade has turned events like the annual meeting of the American Society of Hematology (ASH) into one of the year’s most highly anticipated affairs for industry watchers wanting to get the lowdown on the most exciting blood cancer treatments of tomorrow.
Below is a list of some of the more notable topics coming into the meeting, which took place in San Francisco over the weekend, along with an overview of what was learned...
PD-1s move into haematological malignancies
ASH was expected to be something of a coming out party for immuno-oncology products like Merck & Co.’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab) in the blood cancer space, and the drugs did not disappoint as they generated respective overall response rates (ORR) of 66 percent  and 87 percent  in Phase I studies in heavily pre-treated patients with Hodgkin’s lymphoma (HL). JP Morgan analyst Chris Schott called the activity for both “impressive” and warned against drawing conclusions about their comparative efficacy based on such a small number of heterogeneous patients.
In fact, while many investors went into the meeting looking for differences between Keytruda and Opdivo, it was a notable similarity that may coincidentally have stood out most as a mechanistic study elucidating the role a 9p24 chromosomal mutation plays in elevating PD-L1 levels in HL – but, crucially, not in many other blood cancers, offered a possible explanation why the drugs were effective in HL but less so elsewhere, such as multiple myeloma where data showed Opdivo generated zero responses in 27 patients .
Schott said the commercial opportunity in HL is relatively small, meaning the viability of the drugs in a setting like non-Hodgkin’s lymphoma will be key for Bristol-Myers Squibb and Merck to unlock more upside.
CD38 coming of age
Interest in anti-CD38 antibodies has exploded thanks to big-money deals between Johnson & Johnson and Genmab  as well as Celgene and MorphoSys , which along with an in-house programme from Sanofi are developing the three most advanced programmes in the space. The big winner at this year’s ASH among this group turned out to be daratumumab from Genmab and Johnson & Johnson as Phase I/II data showed it plus Revlimid and dexamethasone (Rd) generated an ORR of 100 percent in relapsed/refractory multiple myeloma (MM) patients, including a 31 percent complete response rate, which compares favourably to the 65 percent ORR reported for Sanofi’s SAR650984. (MorphoSys/Celgene did not present new data in the setting.)
"The maximum tolerated dose had not been reached for SAR650984," noted JP Morgan analyst Richard Vosser, which means Sanofi has some flexibility to try and find a more effective window, though for the moment the "efficacy does not look as strong as daratumumab."
CAR T-cell therapies emerging
A whole host of companies are pursuing therapies that involve reprogramming a patient’s immune system using chimeric antigen receptor (CAR) T-cells, including Juno and Kite to name a few, but the programme that attracted the most buzz at ASH this year was Novartis’ CTL019, which achieved complete responses in 36 (or 92 percent) of 39 paediatric patients with relapsed/refractory acute lymphoblastic leukaemia in a Phase I/IIa study . The agent also generated an ORR in all five follicular lymphoma patients in another study, but only 45 percent in those with diffuse large B cell lymphoma.
Despite the impressive activity, and the build-up of hype surrounding similar successes being reported by companies like Juno and Kite, Vosser is still taking a wait and see approach to CTL019’s commercial prospects. “Overall we continue to be cautious on the potential outside of later lines of therapy due to lack of presence of a safety switch to prevent long term toxic effects of reengineered T cells,” he said, predicting peak sales of just north of $200 million.
Amgen's hit and miss
The meeting had its ups and downs for Amgen, which made a splash in the blood cancer space when it bought Onyx for just over $10 billion  in 2013 but has thus far not been able to generate the kind of clinical data it would need to build MM drug Kyprolis (carfilzomib) – the crown jewel of the deal – into the mega-blockbuster for which it was hoping.
Detailed results from the Phase III ASPIRE study, which had been toplined in a press release earlier this year, presented at ASH showed what the clinician presenting the data called an “unprecedented” improvement on progression-free survival when added to Revlimid and dexamethasone (26.3 months versus 17.6 months for the two-drug control), supported by a trend towards an improvement on overall survival at an interim analysis. As important, and perhaps more so, the data also look reassuring with respect to cardiac and renal adverse events, which were the generally same or lower for the three-drug combination as had been observed in prior single-arm studies with Kyprolis.
The data may further entrench Kyprolis in the relapsed MM setting, and could even help Amgen’s effort to push into earlier-stage patients, but the Street remains cool on the prospects due to the impending emergence of competition from generic versions of Johnson & Johnson’s Velcade, another proteasome inhibitor, as well as Kyprolis’ twice-weekly dosing schedule (versus once-weekly for Velcade). (See Physician Views Poll Results: Oncologists view an up then down week for Kyprolis as a net positive for Amgen's multiple myeloma drug .)
On the other hand, the Street was underwhelmed by new data for Amgen’s oprozomib, an oral proteasome inhibitor also from Onyx, which appears to have some difficulties with grade 3/4 adverse events (including diarrhoea) and lags Takeda’s ixazomib in the race to market.
The king of MM looks to grow its kingdom
Celgene has emerged as a market leader in the haematological malignancy space thanks in large part to the success of its Revlimid (lenalidomide) franchise in MM, but the company now looks to have set its sights on expanding into new arenas, both with internal programmes and via the vast array of partnerships it has been investing over many years.
According to Morgan Stanley analyst Matthew Harrison, one of Celgene’s primary goals is to dip more heavily into the acute myelogenous leukaemia (AML) and myelodysplastic syndromes (MDS) space, which it believes will grow from $850 million today into a “$3 billion business over the next few years.” Part of this plan will involve filing for EU approval of MM drug Vidaza in AML next year.
Also on Celgene’s front burner is its aspirations in the immuno-oncology space, where it highlighted two programmes – an anti-CD47 monoclonal antibody to promote phagocytosis and the TLR8 agonist VTX-2337 – that it plans to combine with an anti-PDL1 agent in ovarian cancer. The company also plans to announce an initial target next year and begin human studies “shortly” via a partnership effort with bluebird bio.