[gdatlc]

Maintenance therapy after allogeneic transplant

by gdatlc on Tue Aug 09, 2011 10:03 am

Anyone out there with any info regarding maintenance therapy after allogeneic bone marrow transplant? Is this advisable, and if so, under what circumstances?

I realize that the number of patients treated with allogeneic transplant is small, but I'm wondering if anyone has had this experience or knows of research resources that might be available to investigate.

[karenh]

Re: Maintenance therapy after allogeneic transplant

by karenh on Tue Aug 09, 2011 1:49 pm

I am wondering about this as well. There is a study at the Fred Hutchinson Center in Seattle using Revlimid as maintenance, but I think results are not in. I did not qualify for this and my doc did not want to do this "off study." (My allo was in 2008 and I'm in remission and not on drugs other than biophosphonate infusions.)

Please stay in touch and share what you learn! I will let you know if I learn anything new.

Karen

[Dr. Edward Libby]

Re: Maintenance therapy after allogeneic transplant

by Dr. Edward Libby on Tue Aug 09, 2011 6:27 pm

There is very little published research on maintenance therapy after allogeneic stem cell transplant for multiple myeloma. A recent trial published in the journal Blood found excessive toxicity (GVHD) when Revlimid was used post allo transplant. Maintenance therapy post allo transplant should probably only be given as part of a research study at this time.

[Beacon Staff]

Re: Maintenance therapy after allogeneic transplant

by Beacon Staff on Fri Mar 20, 2015 10:20 am

There was a question in a recent comment on Steve Mohr's latest column that led us to want to update this thread.

The study that Dr. Libby referred to in his posting above is, we believe, this one:

E Kneppers et al, "Lena­lido­mide main­te­nance after nonmyeloablative allogeneic stem cell trans­plan­ta­tion in multiple myeloma is not feasible: results of the HOVON 76 Trial," Blood, September 2011 (published online June 2011) (link to full text of article)

There has been another study about Revlimid main­te­nance that was published recently. Here is a reference to it:

M Alsina et al, "Lena­lido­mide main­te­nance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell trans­plan­ta­tion," Biology of Blood and Marrow Trans­plan­ta­tion, August, 2014 (link to article abstract)

Here are the abstracts of the two studies.

Kneppers et al, 2011:

To improve the outcome of allogeneic stem cell trans­plan­ta­tion (allo-SCT) in multiple myeloma as part of first-line treatment, we prospectively investigated the feasibility and efficacy of lena­lido­mide main­te­nance. Patients started main­te­nance 1 to 6 months after nonmyeloablative allo-SCT. Lena­lido­mide was dosed 10 mg on days 1 to 21 of a 28-day schedule for a total of 24 cycles. Peripheral blood samples were taken to evaluate immune modulating effects.

Thirty-five eligible patients were enrolled, and 30 started with lena­lido­mide. After 2 cycles, 14 patients (47%) had to stop treatment, mainly because of the development of acute graft versus host disease (GVHD). In total, 13 patients (43%) stopped treatment because of development of GVHD, 5 patients (17%) because of other adverse events, and 5 patients (17%) because of progression. Responses improved in 37% of patients, and the estimated 1-year progression-free survival from start of main­te­nance was 69% (90% confidence interval, 53%-81%). lena­lido­mide increased the frequency of human leukocyte antigen-DR+ T cells and regulatory T cells, without correlation with clinical parameters.

In conclusion, lena­lido­mide main­te­nance 10 mg daily after nonmyeloablative allo-SCT with un­manipu­lated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial was registered at http://www.trialregister.nl as #NTR1645.

Alsina et al, 2014:

Allogeneic hematopoietic cell trans­plan­ta­tion (alloHCT) with reduced-intensity con­di­tion­ing is an appealing option for patients with high-risk multiple myeloma. However, progression after alloHCT remains a challenge. Main­te­nance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect.

The primary objective of this clinical trial was to determine the tolerability and safety profile of main­te­nance lena­lido­mide (LEN) given on days 1 to 21 of 28 days cycles, with intra­patient dose escalation during 12 months / cycles after alloHCT.

Thirty alloHCT recipients (median age, 54 years) with high-risk multiple myeloma were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed main­te­nance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%.

Outcomes at 18 months after initiation of main­te­nance were multiple myeloma pro­gression, 28%; trans­plan­ta­tion-related mortality, 11%; and progression-free and over­all survival, 63% and 78%, respectively.

The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk multiple myeloma population warrant further study of this approach.