The 2017 American Society of Clinical Oncology (ASCO) meeting is in full swing in Chicago. This morning marked the first myeloma oral sessions. Interesting topics included:
- New choices for induction therapy in newly diagnosed patients– adding monoclonal antibodies to approved therapies
- Evaluation of Kyprolis and denosumab as part of frontline therapies
- New triplet therapy choices for relapsed refractory MM patients
New choices for induction therapy in newly diagnosed MM (NDMM):
Dr. Jakubowiak of U Chicago reported on the MMY1001 trial, the addition of Darzalex (daratumumab, dara) to Kyprolis/Revlimid/dexamethasone (KRD) therapy in NDMM patients.
- Dara plus KRD was well tolerated by patients, with dara contributing no additional side effects besides those normally seen with KRD.
- The combination was highly effective, with 100% of treated patients showing a response (91% with a very good partial response or better, and 43% with a complete response or better). However the number of patients treated in this trial was small.
- Addition of dara had no effect on the ability to collect stem cells for later autologous stem cell transplant (ASCT) from the treated patients.
- Although this is a preliminary study with a small sample size, the data warrant further investigation of this regimen as a potential frontline therapy choice.
Dr. Laubach of DanaFarber Cancer Institute reported results of an MMRC trial with 40 patients, combining Empliciti (elotuzumab, Elo) with a Velcade/Revlimid/dexamethasone (VRD) combination in NDMM.
- Elo combined with VRD showed a similar response rate to VRD alone, with 82% of patients showing a response (55% with a very good partial response or better, and 15% with a complete response or better).
- Side effects were higher when Elo was added, as was rate of infection
- Despite side effects, the response rate is promising; side effects may be decreased by changing the dose levels or the dosing schedule of the combination
- This is a small study with preliminary data; results will be confirmed and expanded in additional trials
Kyprolis as part of front line triplet therapy:
- Kyprolis combined with RD (KRD) produces a deeper response than VRD with a longer progression free survival (PFS) in NDMM. This data may eventually lead to approval of KRD as a standard of care induction therapy if this data is confirmed in Ph3 studies.
Denosumab vs Zolendronate (Zometa) for bone loss
- In an update of data first presented at the International Myeloma Workshop in India in early March, denosumab was shown to have efficacy similar to Zometa against bone loss, but showed an 11 month increase in progression free survival vs Zometa, with lower renal toxicity.
- This was a large study comparing results in 850 patients on Denosumab and 850 on Zometa
- Denosumab is a potential new supportive care option, as an alternative to Zometa
New triplet therapies in Relapsed Refractory Multiple Myeloma (RRMM)
- Updated survival results were presented for 2 large studies that included Darzalex with Velcade/dex (CASTOR trial, DVd vs Vd) and Revlimid/dex (POLLUX trial, DRd vs Rd). Inclusion of dara in both trials provided longer progression free survival (PFS) – time before the myeloma came back – and a deeper response, as measured by minimal residual disease (MRD) testing. This improved PFS was shown in both normal risk and high risk patients. In fact, if high risk patients on these trials achieved a deep response, they did not show evidence of disease progression even when followed for a long period of time after treatment. This is a preliminary finding, but if it is confirmed, this regimen could provide significant clinical benefit to high risk MM patients.
- • Isatuximab is similar to Darzalex; both are monoclonal antibodies which bind to the CD38 target on the surface of MM cells. A new study of Isatuximab with Pomalyst and dex showed side effects that were manageable, with a shorter infusion time than Darzalex (4 hours vs 8 hours for the first infusion). The response rate to this regimen was 75% in 26 patients who had received many prior treatments. This data is promising, and more PhIII trials are planned. Isatuximab is also being studied in several MMRC trials, both alone and in combination with other approved agents.
Stay tuned for more updates from ASCO this week!