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What Our Doctors Read Influences How Patients Are Treated – For Now That Means Using Lots Of Drugs & Invasive, Expensive Transplants

Home/What Our Doctors Read Influences How Patients Are Treated – For Now That Means Using Lots Of Drugs & Invasive, Expensive Transplants

What Our Doctors Read Influences How Patients Are Treated – For Now That Means Using Lots Of Drugs & Invasive, Expensive Transplants

What our doctors read in medical journals and publications which summarize research results and new therapy trends greatly influences how they are likely to act.

Case in point:  Here is an article from the trade publication, Internal Medicine News about what is soon to be considered the “standard of care” for multiple myeloma patients:

ORLANDO – For patients with newly diagnosed multiple myeloma, an intensive chemotherapy regimen with bortezomib, lenalidomide, and dexamethasone for induction followed by transplant and consolidation with the same regimen plus lenalidomide maintenance produced high rates of very good partial responses or better, with no major peripheral neuropathies, French investigators reported at the annual meeting of the American Society of Hematology.

Primary results of the phase II IFM 2008 study showed that 80% of patients had at least a very good partial response (VGPR), and nearly 50% of patients had either a stringent complete response (sCR) or complete response (CR) according to international uniform response criteria, said Dr. Murielle Roussel from Hôpital Purpan in Toulouse, France.

There were no cases of grade 3 or 4 peripheral neuropathy, suggesting that the regimen is relatively safe, said Dr. Roussel on behalf of colleagues in the Intergroupe Francophone du Myélome (IFM).

“This intensive program compares favorably to the results obtained with long-term treatment with novel combinations without high-dose therapy. It is, as you know, the framework for the high-dose therapy arm in the IFM/DFCI 2009 joint trial challenging the role of up-front autologous stem cell transplant,” she said.

Evidence from recent clinical trials conducted by the IFM and others suggest that a combination of bortezomib, lenalidomide, and dexamethasone (VRD) is a promising three-drug induction regimen prior to autologous stem cell transplants (ASCT). Consolidation therapy can enhance the depth of response, and maintenance can prolong its duration, supporting the choice of VRD as the backbone for the trial, Dr. Roussel said.

The investigators enrolled 31 patients aged younger than 65 years with newly diagnosed multiple myeloma from eight IFM transplant centers. The patients underwent induction therapy with three cycles of VRD, each lasting 21 days. The regimen included bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11), lenalidomide (25 mg/day for days 1-14), and oral dexamethasone (40 mg on day 1, 8, and 14).

Patients were assessed for response after the third cycle, and peripheral stem cells were mobilized and harvested. They then underwent intensification with melphalan 200 mg/m2 and ASCT. After a 2-month hematologic recovery period, the patients could then receive two cycles of VRD consolidation, followed by a year of lenalidomide maintenance, with the drug given at 10 mg/day for 3 months, with dose escalation up to 15 mg if the lower dose was well tolerated.

The primary study outcome was best achieved response 1 month after consolidation. Secondary end points included response rates after three cycles of VRD, the safety and tolerability of the combination in the setting of high-dose therapy, the feasibility of stem cell harvest, progression-free survival, overall survival, time to progression, and duration of response.

The combined CR and sCR rate after induction was 23%, and 62% of patients had a VGPR or better. Following transplant, those rates rose to 36% and 68%, respectively; after consolidation, they were 48% and 84%.

Common toxicities of all grades included thrombocytopenia in 97% of patients, and anemia and neutropenia each in 87%. Sensory peripheral neuropathy occurred in 68% of patients, erythroderma or skin rash in 32%, pneumonia in 16%, and varicella zoster viral infections in 13%.

In all, 39% of patients experienced grade 3 or 4 neutropenia leading to lenalidomide dose reduction in eight patients (26% of the total cohort). In addition, 13% of patients had grade 3 thrombocytopenia, and 6% had grade 3 anemia. There were no grade 4 thrombocytopenia or anemia cases, and no grade 3 or 4 sensory peripheral neuropathy. Grade 1 or 2 neuropathy requiring reductions of bortezomib dose occurred in seven patients.

From one to five stem cell collections (median, two) were required to obtain a sufficient number for ASCT. Five patients needed a second-line mobilizing agent, and investigators were unable to obtain enough cells from one patient with stable disease; this patient did not undergo autologous transplant.

The IFM-2008 study is sponsored by University Hospital Toulouse, with support from Celgene and Janssen-Cilag. Dr. Roussel disclosed receiving research funding and serving on the speakers bureaus of the companies.

On the surface, this is good news… A previously, barely treatable cancer with no cure now can be slowed in a majority of patients, using a vary invasive treatment regimen which includes lots of chemotherapy and a stem cell transplant, followed by more chemo as maintenance. 
 
Don’t get me wrong.  I’m glad this therapy works.  But so do a lot of others.  Where is the research about how taking less is more?  What about the philosophy to always chose the least invasive treatment option first? 
 
Note the last paragraph of the article:

The IFM-2008 study is sponsored by University Hospital Toulouse, with support from Celgene and Janssen-Cilag. Dr. Roussel disclosed receiving research funding and serving on the speakers bureaus of the companies.

Look, I’m not saying Dr. Roussel is crooked or doesn’t mean well.  But I want to see study results which compare this type intensive, aggressive therapy with a more gradual, “treat the myeloma as you go” regimen. 

Some would argue that is already being done and this type of therapy works best.  But I argue we are comparing apples to oranges here. 

What about taking VRD during induction, then skipping the transplant and watching and waiting?  Or then continuing through consolidation, then watching and waiting?  Or skipping the transplant and going on maintenance? 

In any of these cases–just like the more aggressive therapy–when the myeloma returns, knock it back with the same or modified drug combination, then watch and wait.  Or then stay on maintenance.  Or stay on maintenance for a while, then watch and wait? 

There are so many possible combinations to test here.  But the easiest for a patient and doctor (and drug company) to promote or understand is the most aggressive therapy. 

But is aggressive always best?  And what about the obvious conflict of interests here.

Let me sum it all up this way:  DISAPPOINTING!

Yesterday, a fellow patient and reader, Hanna, asked me this:

So Pat, what are your plans? I believe you are 4 years on maintenance now, right? I’m almost 2. Do you plan do discuss this with your onc? Would you consider getting off REV to give your body a break?

Getting off Revlimid?”  What a novel concept.  How long are we supposed to stay on maintenance?  Patients (me!) and their doctor don’t know how long to continue maintenance.  Six months?  One year?  Two years?  Forever?  How about when the insurance money runs out?

UAMS Total Therapy patients expect to stay on aggressive maintenance, using several different chemotherapy agents, for three years following tandem transplants.  Really?  My guess is many of those patients will decide to stay on a reduced dose, one drug maintenance therapy indefinitely. 

I am not against any of these options if they are the only way to keep myeloma at bay.  But are nuanced research studies being conducted to help us make better choices–even if that means taking less drugs over a shorter period of time–when these studies are funded by the same companies which sell the drugs? 

This thread is definitely not putting me in the holiday spirit!  Tomorrow I will share some more positive holiday thoughts.

Feel good and keep smiling!  Pat