Evaluation of Institutional Non-Core Chemotherapy Regimens Approved for the Treatment of Leukemia and Multiple Myeloma

The University of Wisconsin Chemotherapy Council (UWCC) monitors the uniformity and appropriateness of chemotherapy administration at the University of Wisconsin Hospital and Clinics through a peer-review process.  One aspect involves approval of “patient specific requests” (PSRs) that involve treatments not included in the institution’s core regimens. Providers are asked to submit published evidence, information regarding pt. comorbidities, and clinical justification to support the application. However there is no current stipulation regarding demonstration of value, although implicit in this review process is to avoid futile, expensive or potentially harmful treatments.  Given the ever burgeoning chemotherapeutic choices available for patients with any stage of disease, and the complexity of selecting an optimal therapeutic regimen, we hypothesized that some approved PSRs might have provided limited benefit to the pts who received them.  Therefore, we undertook an analysis of PSRs specifically submitted for patients with leukemia and multiple myeloma (MM) between 1/1/2011 and 7/31/2014 to exam reasons for the submission as well as outcomes after the new therapy was initiated.

 METHODS: A total of 307 PSRs were reviewed by the UWCCC during this time period. Forty-one were specifically submitted and approved for patients with leukemia or MM. Reason for PSR, status at initiation, previous transplant, and days of hospitalization after PSR and 1 year survival were calculated.

Diagnosis	Number	Status at time of PSR	Previous Transplant	Median No previous regimens	Reason for PSR submission	PSR Regimen	Mean Survival After PSR starts	1 yr. survival
AML, relapsed	8	Refractory relapse	88%	3	No SOC1	Various	236d (range 88-575d)	12%
AML, other	2	Remission	0	1	Nonstandard Transplant regimen	Transplant regimen	533 d	100%
CML, relapsed	2	Refractory	No	3	Failed all previous regimens	Transplant regimen	289d	50%
ALL, newly diagnosed	5	Untreated	NA	0	Adult treated on pediatric regimen (n=3); elderly (n=2)	Various	551d (range 365-981d)	100%
ALL, relapsed	5	Relapsed	20%	3 (range 1-8)	No SOC1	CVP2, TKI3 based;, BFM4	408d (range 167-735d)	40%
MM	15	Relapsed, refractory (n=15) 100%	73% (auto)	7 (range 2-10)	Not core regimen (n=13) Rare subtype(n=2)	PCP5 (n=3); CRD6 (n-4) other	272 d ( range 74-661)	60%
APL	4	untreated	N/A	N/A	Not Core Regimen	ATRA/Arsenic, other	788d (range 692-910d)	100%

¹ SOC; ² cyclophosphamide, vincristine prednisone; ³ tyrosine kinase inhibitor; ⁴ Berlin/Frankfurt/Munich; ⁵Pomalidomide, cyclophosphamide, prednisone; ⁶carfilzomib, lenalidomide dexamethasone

RESULTS: A total of 41 PSRs were examined. The most common reasons for submission of the PSR was request for a non-core regimen including a recently FDA approved use of an agent (n= 11); no current SOC established (n=13); salvage therapy with older regimen ((n=2). Median 1 yr. survival varied from 12% to 100% depending on diagnosis. Not surprisingly, APL pts displayed the best overall survival, followed by AML, transplanted with a nonstandard conditioning regimen.   AML patients relapsing after previous allogeneic transplant had the worst survival, regardless of salvage regimen; only 1 pt. survived longer than 6 months. The median length of hospital stay in these patients following start of PSR was 43 d (range 14-54).  Relapsed ALL pts also fared poorly, with 1 year survival of 40% and median days of hospitalization after PSR of 48d (range 0-117). Relapsed refractory MM pts had a variable outcome, with some pts surviving more than 3 years and others for only several months.

CONCLUSION: Use of peer reviewed PSRs resulted in reasonable outcomes in most patients with leukemia and myeloma. However, pts with AML relapsing after allogeneic transplant and those with relapsed ALL fared particularly poorly despite treatment with a peer reviewed treatment plan, presumably chosen for best outcome. Furthermore, these salvage treatments were associated with lengthy hospital stays. Such patients are unlikely to benefit from any currently available regimens and may be more appropriately considered for clinical trials or supportive/ palliative care at time of relapse.