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Lenalidomide Desensitization in Systemic Light-Chain Amyloidosis With Multi-Organ Involvement.

Seki JT, Sakurai N, Kukreti V - J Clin Med Res (2015)

Bottom Line: Lowering lenalidomide doses have not been able to consistently prevent recurrent skin toxicity.To the best of our knowledge, this was the first AL patients who received and tolerated RDP well, despite multi-organ impairments.Incremental dose increase can be applied in future dates without risk of rash recurrence.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Princess Margaret Hospital, Toronto, ON, Canada ; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada ; College of Pharmacy and Health Sciences, Drake University, Des Moines, IA, USA.

ABSTRACT
Limited therapeutic options are available to amyloid patients treated with many lines of therapy. Although combination therapy using lenalidomide and dexamethasone is an effective sequential regimen for systemic amyloidosis (AL), dexamethasone is often poorly tolerated in patients with cardiac involvement. Lenalidomide as single agent has modest activity, but when used in combination with dexamethasone, careful titration is needed. Dermatological adverse reactions can be problematic to patients on lenalidomide-based therapy. Lowering lenalidomide doses have not been able to consistently prevent recurrent skin toxicity. We report a patient who was neither eligible for stem cell transplant nor able to tolerate previous lines of therapy. Therapeutic dilemma arose from lenalidomide-related moderately severe skin toxicity. We enrolled the patient in the lenalidomide rapid desensitization program (RDP) with success in the presence of poor cardiac reserve and renal impairment. No recurrence of skin rash was observed during the course of therapy. To the best of our knowledge, this was the first AL patients who received and tolerated RDP well, despite multi-organ impairments. The target dose may be achieved based on individual patient's ability to tolerate RDP. Incremental dose increase can be applied in future dates without risk of rash recurrence.

No MeSH data available.


Related in: MedlinePlus

Combined results of troponin and BNP throughout the course of treatment.
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Figure 1: Combined results of troponin and BNP throughout the course of treatment.

Mentions: Our patient was not eligible for autologous stem cell transplant, but instead she received melphalan and dexamethasone which began in July 2009. She developed thrombocytopenia on the seventh cycle as dose limiting toxicity that required therapy discontinuation. She had achieved partial response (PR) as per hematologic response criteria (Table 1) [4]. Although BNP levels (baseline 2,708.1 pg/mL) continued to decline from the start of treatment, troponin level was persistently elevated (baseline 0.08 μg/L) (Fig. 1). Her disease progressed by July 2010. Proteasome inhibitor (PI) bortezomib and dexamethasone weekly combination regimen was initiated. Granted that this chemotherapy regimen has made very good partial response (VGPR) by April 2011 (Table 1), she had been experiencing several side effects (grade 3) including diarrhea, severe fatigue and peripheral neuropathy. Bortezomib-related neuropathic changes cannot be ruled out, although her baseline neurological exams were unremarkable prior to the start of therapy. During this time, BNP levels were persistently decreasing, while troponin levels reached its maximum (0.18 μg/L) 2 months after bortezomib treatment began (Fig. 1). She was not tolerating bortezomib despite dose reduction to 1 mg/m2. PI was discontinued after completing the fifth cycle in April 2011. Due to bortezomib-related complications, she was not willing to proceed further with treatment. Interestingly during the next 29 months treatment-free period, BNP and troponin levels maintained below 672.6 pg/mL and 0.07 μg/L respectively (Fig. 1). NYHA classification was sustained at level 2. It was not until a sharp rise in her free kappa and lambda levels by October 2013 (Fig. 2), where she then consented to commence single agent lenalidomide starting at 5 mg every other day (21 days out of a 28 day cycle), in the presence of cardiac symptoms and reduced creatinine clearance of less than 30 mL/min. On the fifth day of therapy at home, she developed a moderately severe rash (grade 3 - 4) which was maculopapular in nature affecting more than 50% of body surface area involving her mouth, palms, soles, underneath the axillae, groin, back of her legs and also on the torso. She experienced pruritus, fatigue and mild weight loss. The rash was completely resolved within 3 days after discontinuation of lenalidomide. An in-patient oral RDP was used due to limited therapeutic options for this patient and the desire to maximize lenalidomide therapy in December 2013 (Supplementary 1, http://www.jocmr.org; Table 2). She received a cumulative dose of 2.65 mg of lenalidomide. The entire procedure took 4.5 h to complete in the in-patient setting. She was stable and did not experience any adverse events. She began with a dose of 1 mg every other day over the next 8 days. She also tolerated dose escalation well with lenalidomide 2 mg every other day, and over the next 21 days. As time progressed, her dose was increased to lenalidomide 5 mg every other day in January 2014 without any complications. She had achieved a PR (Table 1).


Lenalidomide Desensitization in Systemic Light-Chain Amyloidosis With Multi-Organ Involvement.

Seki JT, Sakurai N, Kukreti V - J Clin Med Res (2015)

Combined results of troponin and BNP throughout the course of treatment.
© Copyright Policy - open access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554222&req=5

Figure 1: Combined results of troponin and BNP throughout the course of treatment.
Mentions: Our patient was not eligible for autologous stem cell transplant, but instead she received melphalan and dexamethasone which began in July 2009. She developed thrombocytopenia on the seventh cycle as dose limiting toxicity that required therapy discontinuation. She had achieved partial response (PR) as per hematologic response criteria (Table 1) [4]. Although BNP levels (baseline 2,708.1 pg/mL) continued to decline from the start of treatment, troponin level was persistently elevated (baseline 0.08 μg/L) (Fig. 1). Her disease progressed by July 2010. Proteasome inhibitor (PI) bortezomib and dexamethasone weekly combination regimen was initiated. Granted that this chemotherapy regimen has made very good partial response (VGPR) by April 2011 (Table 1), she had been experiencing several side effects (grade 3) including diarrhea, severe fatigue and peripheral neuropathy. Bortezomib-related neuropathic changes cannot be ruled out, although her baseline neurological exams were unremarkable prior to the start of therapy. During this time, BNP levels were persistently decreasing, while troponin levels reached its maximum (0.18 μg/L) 2 months after bortezomib treatment began (Fig. 1). She was not tolerating bortezomib despite dose reduction to 1 mg/m2. PI was discontinued after completing the fifth cycle in April 2011. Due to bortezomib-related complications, she was not willing to proceed further with treatment. Interestingly during the next 29 months treatment-free period, BNP and troponin levels maintained below 672.6 pg/mL and 0.07 μg/L respectively (Fig. 1). NYHA classification was sustained at level 2. It was not until a sharp rise in her free kappa and lambda levels by October 2013 (Fig. 2), where she then consented to commence single agent lenalidomide starting at 5 mg every other day (21 days out of a 28 day cycle), in the presence of cardiac symptoms and reduced creatinine clearance of less than 30 mL/min. On the fifth day of therapy at home, she developed a moderately severe rash (grade 3 - 4) which was maculopapular in nature affecting more than 50% of body surface area involving her mouth, palms, soles, underneath the axillae, groin, back of her legs and also on the torso. She experienced pruritus, fatigue and mild weight loss. The rash was completely resolved within 3 days after discontinuation of lenalidomide. An in-patient oral RDP was used due to limited therapeutic options for this patient and the desire to maximize lenalidomide therapy in December 2013 (Supplementary 1, http://www.jocmr.org; Table 2). She received a cumulative dose of 2.65 mg of lenalidomide. The entire procedure took 4.5 h to complete in the in-patient setting. She was stable and did not experience any adverse events. She began with a dose of 1 mg every other day over the next 8 days. She also tolerated dose escalation well with lenalidomide 2 mg every other day, and over the next 21 days. As time progressed, her dose was increased to lenalidomide 5 mg every other day in January 2014 without any complications. She had achieved a PR (Table 1).

Bottom Line: Lowering lenalidomide doses have not been able to consistently prevent recurrent skin toxicity.To the best of our knowledge, this was the first AL patients who received and tolerated RDP well, despite multi-organ impairments.Incremental dose increase can be applied in future dates without risk of rash recurrence.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Princess Margaret Hospital, Toronto, ON, Canada ; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada ; College of Pharmacy and Health Sciences, Drake University, Des Moines, IA, USA.

ABSTRACT
Limited therapeutic options are available to amyloid patients treated with many lines of therapy. Although combination therapy using lenalidomide and dexamethasone is an effective sequential regimen for systemic amyloidosis (AL), dexamethasone is often poorly tolerated in patients with cardiac involvement. Lenalidomide as single agent has modest activity, but when used in combination with dexamethasone, careful titration is needed. Dermatological adverse reactions can be problematic to patients on lenalidomide-based therapy. Lowering lenalidomide doses have not been able to consistently prevent recurrent skin toxicity. We report a patient who was neither eligible for stem cell transplant nor able to tolerate previous lines of therapy. Therapeutic dilemma arose from lenalidomide-related moderately severe skin toxicity. We enrolled the patient in the lenalidomide rapid desensitization program (RDP) with success in the presence of poor cardiac reserve and renal impairment. No recurrence of skin rash was observed during the course of therapy. To the best of our knowledge, this was the first AL patients who received and tolerated RDP well, despite multi-organ impairments. The target dose may be achieved based on individual patient's ability to tolerate RDP. Incremental dose increase can be applied in future dates without risk of rash recurrence.

No MeSH data available.


Related in: MedlinePlus