This afternoon's oral sessions on myeloma featured four
much-anticipated studies: Antonio Palumbo's (University of Torino, Italy) report
on his VMPT-VT vs. VMP trial for 511 newly diagnosed patients ineligible for
transplant (abstract 22); Martha Lacy's (Mayo Clinic, Rochester, MN) summary of
data from 6 phase II trials at Mayo with pomalidomide and dexamethasone for 345
patients with relapsed/refractory myeloma (abstract 201); Paul Richardson's (Dana-Farber
Cancer Institute, Boston, MA) report on the phase II study of the monoclonal
antibody elotuzumab + len/dex for relapsed/refractory disease; and Michael
Savona's (Sarah Canon Research Institute, Nashville, TN) presentation of the
phase Ib dose-escalation study of oprozomib (Onyx's oral proteasome
inhibitor).
The four-drug regimen of VMPT-VT, which is VMPT Velcade,
melphalan, prednisone, and thalidomide with two years of maintenance with
Velcade and thalidomide, out-performed triplet VMP with no maintenance, the
current standard of care in Europe, both in PFS and OS. Dr. Palumbo
demonstrated that the 4-drug regimen with continuous therapy provided better
disease control. Due to toxicities in
the elderly (>75 years) patients, however, it is a better regimen for those
age 65-75.
Dr Lacy's presentation, a model of clarity and fluency,
covered data on pom/dex studies performed at Mayo between 2007 and 2012. Although dosing and eligibility criteria
varied among the studies, the patients were heavily pretreated, 40% had
abnormal cytogenetics, 17% had 17p deletion, and 44% were high risk. Even in this population, the overall response
rate of PR or better was 35%. When asked, Dr. Lacy explained that the key
differences between lenalidomide and pomalidomide are 1) pomalidomide can work
in patients who are refractory to lenalidomide; 2) there is much less
myelosuppression (impairment of the bone marrow's ability to make new blood
cells) with pomalidomide than with lenalidomide, and 3) pomalidomide does not
cause skin rash, as lenalidomide sometimes does.
Dr. Richardson's review of the data from the phase II study
of elotuzumab +len/dex was also extremely encouraging. In this study, a 10 mg/kg intravenous dose of
the monoclonal antibody was compared with a 20 mg/kg dose. We were all surprised to learn that the
overall response rate in the 10 mg/kg group was 92% in this relapsed and
refractory population, while the response rate in the patients treated with 20
mg/kg was 76%. Sometimes, less really is
more! Responses were very rapid with
either dose: one month for response and two months for best response. PFS has not yet been reached in the 10 mg/kg
group. We expect to see more of this drug in various combination studies that
are ongoing.
We ended our day at the foreign journalists' workshop, where
we were moved by the stories of four patients who have surmounted many
obstacles with a combination of good therapy, good luck, and personal pluck.
They are a testament to the will to live well and fully and to the
effectiveness of novel therapies. The workshop also featured updates on
research that has been or will be presented at the ASH meeting highlighted by
Drs. Brian Durie, Paul Richardson, Robert Orlowski, and Xavier Leleu, followed
by questions from foreign journalists.
There was also an impassioned plea to the press from Brazilian myeloma
specialist Dr. Vania Hungria to advocate for the approval of Revlimid in
Brazil. Those of us who live in
countries where we have access to the latest treatments must never take that
access for granted. It is heartbreaking
that effective new therapies continue to be developed but are not available to
patients in many parts of the world.
