[HHH]

Hyper-CVAD for patient in weakened state - good idea?

by HHH on Tue Oct 07, 2014 10:24 pm

My husband was diagnosed with multiple myeloma with 17p deletion and started Velcade and dex in June. He then had a bowel perforation and emergency surgery in July. Myeloma treat­ment stopped for 4 weeks so he could heal from the surgery.

Multiple myeloma treatment resumed in August with VRD. His SPEP [M-spike] was at 3.6 g/dL (36 g/L) in August. By September 9, the SPEP was down to 1.45 g/dL and blood counts were improving. But two weeks later bloods counts were deteriorating and his back pain returned. He continued to lose weight and get weaker.

His doctor repeated SPEP on Sept 30 and it spiked back up to 3.3 g/dL. Blood counts are bad, creatinine is 3.6. Conclusion today is that the VRD is no longer working. The doctor and the stem cell transplant (SCT) specialist are advising hyper-CVAD with an autologous SCT as the eventual goal.

Is this the right next step? Can a patient in a very weakened state handle hyper-CVAD?

Is the 17p deletion the likely reason that the VRD is not working? Or could it be because we started chemo and then stopped for a month?

Moderator's Note:

For those unfamiliar with Hyper-CVAD, here's a quick description from Wikipedia (link to full article):

Hyper-CVAD chemotherapy consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimize side effects. 'CVAD' is the acronym of the drugs used in course A: cyclophosphamide, vincristine, doxorubicin (also known by its trade name, Adriamycin), and dexamethasone. Course B consists of methotrexate and cytarabine. The protocol was originally developed to treat leukemia in young, fit patients, due to its intensity, but has since begun to be used more widely."

There's a previous discussion of CVAD-based regimens here in the forum here:

"Modified CVAD," Beacon forum discussion started Dec 14, 2013.

[Dr. Prashant Kapoor]

Re: Hyper-CVAD for patient in weakened state - good idea?

by Dr. Prashant Kapoor on Thu Oct 09, 2014 2:46 am

I am sorry to hear about your husband’s pro­gres­sive myeloma. Multiple myeloma with del 17p can be a challenging con­di­tion to treat, and can be particularly taxing on the family members or caregivers . With high risk myeloma, achieving complete remission (CR) is the short-term goal as attainment of CR translates to superior outcome.

HyperCVAD is a tough regimen that is used to manage a variety of aggressive blood cancers, primarily acute lymphoblastic leukemia and certain lymphomas, such as Burkitt’s lymphoma or mantle cell lymphoma. It was shown to be somewhat effective in VAD (vincristine, adria­my­cin and dexamethasone) resistant myeloma by the MD Anderson group almost 20 years ago, prior to the introduction of novel agents, and requires GCSF (growth factor, e.g. Neu­po­gen) support to boost up the counts. It uses a fractionated schedule of cyclo­phos­pha­mide (twice daily). The regimen for myeloma does not utilize methotrexate or cytarabine.

Several factors need to be taken into account prior to considering any aggressive regimen, including patient’s age, comorbidities (such as renal failure, heart dysfunction, ...), patient’s performance status / fitness or ability to carry out activities of daily living, blood counts, etc.

The 3 drugs that your husband’s myeloma has been exposed to so far are Velcade, Revlimid and dexamethasone. Trial of a cyclophosphamide-based combinations (dose-adjusted for renal failure) would be reasonable. However, there are multiple regimens that utilize cyclo­phos­pha­mide, including CyBorD, which may be better tolerated. It is also important to figure out what the cause of low counts and renal failure is – is it the myeloma, treatment-related complications, or other issues? – prior to embarking on further therapy.

The key would be to use an effective regimen to gain sufficient disease control to proceed with stem cell collection and transplantation. Unfortunately, enrollment in a clinical trial may not be possible due to kidney dysfunction, as most trials exclude patients with severe kidney dys­function.

These complex issues obviously cannot be addressed in a forum such as this one. Seeking an opinion at a center of excellence would be the next step, unless he is already at one.

I wish you all the best.