A Phase II Trial of TBL 12 Sea Cucumber Extract In Patients with Untreated Asymptomatic Myeloma

Patients with smoldering multiple myeloma (MM) may remain asymptomatic(ASx) for variable amounts of time and are therefore typicallymonitored without treatment. Chemoprevention trials using thalidomidefound prohibitive toxicity and longer follow up is needed forearly systemic treatment with lenalidomide/dexamethasone ofhigh risk ASxMM. Based on encouraging preclinical data withbioactive food supplements in MM curcumin (Blood 2003), resveratrol(Blood 2006), and a component of green tea extract (Blood 2006)many patients are already using these agents without definitiveproof of efficacy or safety. Preclinically, sphingolipids/glycosidescontained in sea cucumbers have also demonstrated antitumorproperties including antiangiogenesis direct tumor cytotoxicity,and also of particular relevance to MM, the inhibition of osteoclastogenesis.TBL12, an extract of sea cucumber, has been commercially availablesince 1981 and used by human subjects as a food supplement withoutany reported toxicities. We therefore designed a pilot phaseII study to determine the safety and efficacy of TBL12 in patientswith ASxMM.

Methods: Patients were required to have ASxMM with measurable disease,defined as serum m spike ≥ 1 g/dL and/or urine m spike ≥ 200 mg/24hours. If non-secretory, patients were required to have abnormalfree light chains (FLC). A total of 20 patients with ASxMM weregiven TBL12, formulated as a liquid gel (manufactured by UnicornPacific Corporation, IND 103,543) to be kept frozen until thetime of consumption. Patients ingested 2 units of 20 ml twiceper day, for a total of 80 units per day. Disease parameterswere monitored monthly and treatment was continued until progressionof disease (PD).

Results: 23 patients were screened, with 3 failures, and the remaining20 patients proceeded with study treatment. The median age ofthe patient was 58 years (range 22–75), with 11 malesand 9 females. The phenotypes were 14 IgG, 5 Ig A, and one kappalight chain. Generally, this was a high risk ASxMM population,with 14 patients having a serum m spike ≥ 3 g/dl and bone marrowplasma cells (PC) ≥ 10%. The median bone marrow PC involvementfor all patients was 38% (range 10 to 90). (With the additionalhigh risk criteria of a FLC ratio <0.125 or >8, 13 patientswere high risk.) Of the remaining 6 patients, all had immunoparesisand 4 had markedly elevated FLC ratios (range 307-incalculable)and the remaining 2 patients had 9.2 g of bence jones proteinuria(BJP) and an IgA phenotype.

Compliance was excellent and the treatment was well toleratedwith only grade 1 nausea. There was one SAE, a pneumococcalpneumonia requiring admission, which was felt to be unrelatedto study treatment. A total of 11 patients remain on treatment,having completed a median of 11 monthly cycles of TBL12 (range6–17 cycles). The best response to date has been stabledisease. Notably, one high risk patient demonstrated a flatteningin the rate of rise of the m spike concordant with the initiationof study treatment (see Figure 1).

A Phase II Trial of TBL 12 Sea Cucumber Extract In Patients Withuntreated Asymptomatic Myeloma

Figure 1: Best fit line for serum m spike in a patient pre and post TBL12

6 patients came off study for PD after a median of 6.5 cycles(range 2–10). The reasons for PD include: 1 hypercalcemia,1 acute renal insufficiency (after 2 cycles with 9.2g BJP atscreening), 1 for anemia (after 3 cycles with 90% marrow PCat screening), and 1 for a new bony lesion on MRI. 2 patientswithdrew consent after cycle 6 and 8, and 1 was removed aftercycle 13 due to investigator discretion after the pneumoniaSAE.

-1 year I + 1 year

TBL 12 initiated

Conclusions: In this pilot study of high risk ASxMM patients, TBL12 was welltolerated and 11 patients (65%)remain on treatment. The expectedrate of progression for this population from diagnosis is 52%at 2 years, however, the median time to progression has notbeen yet reached in this study. Additional follow up is requiredand data will be updated at the annual meeting. The decreasein the rate of rise in the m-spike in a high risk patient concomitantwith the initiation of study treatment is suggestive of a biologiceffect of TBL12 in MM and warrants further study of TBL 12 ina larger cohort of patients.

Amitabha Mazumder, MD*,1, Ajai Chari, MD2, Lauren Ditrio*,3, Zachary Galitzeck*,4 and Sundar Jagannath, MD5

1 NYU Comprehensive Cancer Center, New York, NY, USA,
2 Mount Sinai School of Medicine, New York, NY, USA,
3 Mount Sinai School Of Medicine, New York, NY, USA,
4 Beth Israel Comprehensive Cancer Center,
5 Multiple Myeloma Program, Mount Sinai Medical Center, New York, NY, USA

Disclosures: No relevant conflicts of interest to declare.

Blood (ASH Annual Meeting Abstracts) 2010 116: Abstract 5042
© 2010 American Society of Hematology

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Abstract 5042

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